Polymorphic cells that form cartilage.
A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.
A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.
The area between the EPIPHYSIS and the DIAPHYSIS within which bone growth occurs.
A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.
A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.
A secreted matrix metalloproteinase that plays a physiological role in the degradation of extracellular matrix found in skeletal tissues. It is synthesized as an inactive precursor that is activated by the proteolytic cleavage of its N-terminal propeptide.
Large HYALURONAN-containing proteoglycans found in articular cartilage (CARTILAGE, ARTICULAR). They form into aggregates that provide tissues with the capacity to resist high compressive and tensile forces.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The formation of cartilage. This process is directed by CHONDROCYTES which continually divide and lay down matrix during development. It is sometimes a precursor to OSTEOGENESIS.
Glycoproteins which have a very high polysaccharide content.
A non-fibrillar collagen found primarily in terminally differentiated hypertrophic CHONDROCYTES. It is a homotrimer of three identical alpha1(X) subunits.
A SOXE transcription factor that plays a critical role in regulating CHONDROGENESIS; OSTEOGENESIS; and male sex determination. Loss of function of the SOX9 transcription factor due to genetic mutations is a cause of CAMPOMELIC DYSPLASIA.
Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).
Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine.
A slowly growing malignant neoplasm derived from cartilage cells, occurring most frequently in pelvic bones or near the ends of long bones, in middle-aged and old people. Most chondrosarcomas arise de novo, but some may develop in a preexisting benign cartilaginous lesion or in patients with ENCHONDROMATOSIS. (Stedman, 25th ed)
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.
Noninflammatory degenerative disease of the knee joint consisting of three large categories: conditions that block normal synchronous movement, conditions that produce abnormal pathways of motion, and conditions that cause stress concentration resulting in changes to articular cartilage. (Crenshaw, Campbell's Operative Orthopaedics, 8th ed, p2019)
Pathological processes involving the chondral tissue (CARTILAGE).
An extracellular endopeptidase of vertebrate tissues similar to MATRIX METALLOPROTEINASE 1. It digests PROTEOGLYCAN; FIBRONECTIN; COLLAGEN types III, IV, V, and IX, and activates procollagenase. (Enzyme Nomenclature, 1992)
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures.
Salts of alginic acid that are extracted from marine kelp and used to make dental impressions and as absorbent material for surgical dressings.
Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.
A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. It is found in the UMBILICAL CORD, in VITREOUS BODY and in SYNOVIAL FLUID. A high urinary level is found in PROGERIA.
The process of bone formation. Histogenesis of bone including ossification.
Cartilage of the EAR AURICLE and the EXTERNAL EAR CANAL.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Abnormal development of cartilage and bone.
General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).
The five long bones of the METATARSUS, articulating with the TARSAL BONES proximally and the PHALANGES OF TOES distally.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
In horses, cattle, and other quadrupeds, the joint between the femur and the tibia, corresponding to the human knee.
PROTEOGLYCANS-associated proteins that are major components of EXTRACELLULAR MATRIX of various tissues including CARTILAGE; and INTERVERTEBRAL DISC structures. They bind COLLAGEN fibers and contain protein domains that enable oligomer formation and interaction with other extracellular matrix proteins such as CARTILAGE OLIGOMERIC MATRIX PROTEIN.
A sugar acid formed by the oxidation of the C-6 carbon of GLUCOSE. In addition to being a key intermediate metabolite of the uronic acid pathway, glucuronic acid also plays a role in the detoxification of certain drugs and toxins by conjugating with them to form GLUCURONIDES.
An extracellular endopeptidase which excises a block of peptides at the amino terminal, nonhelical region of the procollagen molecule with the formation of collagen. Absence or deficiency of the enzyme causes accumulation of procollagen which results in the inherited connective tissue disorder--dermatosparaxis. EC 3.4.24.14.
A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.
A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.
Term used to designate tetrahydroxy aldehydic acids obtained by oxidation of hexose sugars, i.e. glucuronic acid, galacturonic acid, etc. Historically, the name hexuronic acid was originally given to ascorbic acid.
A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III.
A fibril-associated collagen usually found crosslinked to the surface of COLLAGEN TYPE II fibrils. It is a heterotrimer containing alpha1(IX), alpha2(IX) and alpha3(IX) subunits.
Methods for maintaining or growing CELLS in vitro.
A synovial hinge connection formed between the bones of the FEMUR; TIBIA; and PATELLA.
The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united.
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
A ubiquitously expressed, secreted protein with bone resorption and renal calcium reabsorption activities that are similar to PARATHYROID HORMONE. It does not circulate in appreciable amounts in normal subjects, but rather exerts its biological actions locally. Overexpression of parathyroid hormone-related protein by tumor cells results in humoral calcemia of malignancy.
A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.
The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.
A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION.
Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.
A reverse developmental process in which terminally differentiated cells with specialized functions revert back to a less differentiated stage within their own CELL LINEAGE.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the FIBULA laterally, the TALUS distally, and the FEMUR proximally.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.
A type of CARTILAGE characterized by a homogenous amorphous matrix containing predominately TYPE II COLLAGEN and ground substance. Hyaline cartilage is found in ARTICULAR CARTILAGE; COSTAL CARTILAGE; LARYNGEAL CARTILAGES; and the NASAL SEPTUM.
Also known as articulations, these are points of connection between the ends of certain separate bones, or where the borders of other bones are juxtaposed.
A set of twelve curved bones which connect to the vertebral column posteriorly, and terminate anteriorly as costal cartilage. Together, they form a protective cage around the internal thoracic organs.
Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.
A family of low-molecular weight, non-histone proteins found in chromatin.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses.
Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
An autosomal dominant disorder that is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, GENU VARUM, and trident hand. (Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#100800, April 20, 2001)
Inorganic salts of sulfuric acid.
A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The maximum compression a material can withstand without failure. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed, p427)
Major component of chondrocyte EXTRACELLULAR MATRIX of various tissues including bone, tendon, ligament, SYNOVIUM and blood vessels. It binds MATRILIN PROTEINS and is associated with development of cartilage and bone.
Water swollen, rigid, 3-dimensional network of cross-linked, hydrophilic macromolecules, 20-95% water. They are used in paints, printing inks, foodstuffs, pharmaceuticals, and cosmetics. (Grant & Hackh's Chemical Dictionary, 5th ed)
A technique for maintaining or growing TISSUE in vitro, usually by DIFFUSION, perifusion, or PERFUSION. The tissue is cultured directly after removal from the host without being dispersed for cell culture.
A family of intercellular signaling proteins that play and important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.
A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.
A genetic or pathological condition that is characterized by short stature and undersize. Abnormal skeletal growth usually results in an adult who is significantly below the average height.
A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.
An enzyme that catalyzes the random hydrolysis of 1,4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate. (From Enzyme Nomenclature, 1992) There has been use as ANTINEOPLASTIC AGENTS to limit NEOPLASM METASTASIS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.
A plant genus in the LAURACEAE family. The tree, Persea americana Mill., is known for the Avocado fruit, the food of commerce.
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
Membrane proteins that are involved in the active transport of phosphate.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
A subclass of closely-related SOX transcription factors. In addition to a conserved HMG-BOX DOMAIN, members of this group contain a leucine zipper motif which mediates protein DIMERIZATION.
A long, narrow, and flat bone commonly known as BREASTBONE occurring in the midsection of the anterior thoracic segment or chest region, which stabilizes the rib cage and serves as the point of origin for several muscles that move the arms, head, and neck.
The posterior process on the ramus of the mandible composed of two parts: a superior part, the articular portion, and an inferior part, the condylar neck.
A fibrillar collagen found primarily in interstitial CARTILAGE. Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits.
Unstable isotopes of sulfur that decay or disintegrate spontaneously emitting radiation. S 29-31, 35, 37, and 38 are radioactive sulfur isotopes.
The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.
Inflammation of a bone and its overlaying CARTILAGE.
A parathyroid hormone receptor subtype that recognizes both PARATHYROID HORMONE and PARATHYROID HORMONE-RELATED PROTEIN. It is a G-protein-coupled receptor that is expressed at high levels in BONE and in KIDNEY.
Bone in humans and primates extending from the SHOULDER JOINT to the ELBOW JOINT.
A cytokine with both pro- and anti-inflammatory actions that depend upon the cellular microenvironment. Oncostatin M is a 28 kDa monomeric glycoprotein that is similar in structure to LEUKEMIA INHIBITORY FACTOR. Its name derives from the the observation that it inhibited the growth of tumor cells and augmented the growth of normal fibroblasts.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
The longest and largest bone of the skeleton, it is situated between the hip and the knee.
Proteoglycans consisting of proteins linked to one or more CHONDROITIN SULFATE-containing oligosaccharide chains.
Proteases which use a metal, normally ZINC, in the catalytic mechanism. This group of enzymes is inactivated by metal CHELATORS.
An articulation between the condyle of the mandible and the articular tubercle of the temporal bone.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A copper-containing dye used as a gelling agent for lubricants, for staining of bacteria and for the dyeing of histiocytes and fibroblasts in vivo.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.
An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.
A mucopolysaccharide constituent of chondrin. (Grant & Hackh's Chemical Dictionary, 5th ed)
A physiologically active metabolite of VITAMIN D. The compound is involved in the regulation of calcium metabolism, alkaline phosphatase activity, and enhances the calcemic effect of CALCITRIOL.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Elements of limited time intervals, contributing to particular results or situations.
The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Cloning of a novel gene specifically expressed in clonal mouse chondroprogenitor-like EC cells, ATDC5. (1/3820)

We cloned a full-length cDNA encoding a novel mouse protein, A-C2, by differential display method using mouse embryonic fibroblast C3H10T1/2 cells and mouse chondroprogenitor-like EC cells, ATDC5. The deduced amino acid sequence of A-C2 consisted of 106 amino acids with no significant homology to the sequences previously reported. Northern blot analysis showed two major bands of 2.1 and 1.8 kb sizes. Expression of A-C2 mRNA was exclusive to ATDC5 cells at their undifferentiated stage. None of ATDC5 cells at their differentiated stage and adult mice tissues examined expressed A-C2 gene.  (+info)

Inhibition of transforming growth factor beta production by nitric oxide-treated chondrocytes: implications for matrix synthesis. (2/3820)

OBJECTIVE: Nitric oxide (NO) is generated copiously by articular chondrocytes activated by interleukin-1beta (IL-1beta). If NO production is blocked, much of the IL-1beta inhibition of proteoglycan synthesis is prevented. We tested the hypothesis that this inhibitory effect of NO on proteoglycan synthesis is secondary to changes in chondrocyte transforming growth factor beta (TGFbeta). METHODS: Monolayer, primary cultures of lapine articular chondrocytes and cartilage slices were studied. NO production was determined as nitrite accumulation in the medium. TGFbeta bioactivity in chondrocyte- and cartilage-conditioned medium (CM) was measured with the mink lung epithelial cell bioassay. Proteoglycan synthesis was measured as the incorporation of 35S-sodium sulfate into macromolecules separated from unincorporated label by gel filtration on PD-10 columns. RESULTS: IL-1beta increased active TGFbeta in chondrocyte CM by 12 hours; by 24 hours, significant increases in both active and latent TGFbeta were detectable. NG-monomethyl-L-arginine (L-NMA) potentiated the increase in total TGFbeta without affecting the early TGFbeta activation. IL-1beta stimulated a NO-independent, transient increase in TGFbeta3 at 24 hours; however, TGFbeta1 was not changed. When NO synthesis was inhibited with L-NMA, IL-1beta increased CM concentrations of TGFbeta1 from 24-72 hours of culture. L-arginine (10 mM) reversed the inhibitory effect of L-NMA on NO production and blocked the increases in TGFbeta1. Anti-TGFbeta1 antibody prevented the restoration of proteoglycan synthesis by chondrocytes exposed to IL-1beta + L-NMA, confirming that NO inhibition of TGFbeta1 in IL-1beta-treated chondrocytes effected, in part, the decreased proteoglycan synthesis. Furthermore, the increase in TGFbeta and proteoglycan synthesis seen with L-NMA was reversed by the NO donor S-nitroso-N-acetylpenicillamide. Similar results were seen with cartilage slices in organ culture. The autocrine increase in CM TGFbeta1 levels following prior exposure to TGFbeta1 was also blocked by NO. CONCLUSION: NO can modulate proteoglycan synthesis indirectly by decreasing the production of TGFbeta1 by chondrocytes exposed to IL-1beta. It prevents autocrine-stimulated increases in TGFbeta1, thus potentially diminishing the anabolic effects of this cytokine in chondrocytes.  (+info)

Expression of both P1 and P2 purine receptor genes by human articular chondrocytes and profile of ligand-mediated prostaglandin E2 release. (3/3820)

OBJECTIVE: To assess the expression and function of purine receptors in articular chondrocytes. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to screen human chondrocyte RNA for expression of P1 and P2 purine receptor subtypes. Purine-stimulated prostaglandin E2 (PGE2) release from chondrocytes, untreated or treated with recombinant human interleukin-1alpha (rHuIL-1alpha), was assessed by radioimmunoassay. RESULTS: RT-PCR demonstrated that human articular chondrocytes transcribe messenger RNA for the P1 receptor subtypes A2a and A2b and the P2 receptor subtype P2Y2, but not for the P1 receptor subtypes A1 and A3. The P1 receptor agonists adenosine and 5'-N-ethylcarboxamidoadenosine did not change PGE2 release from chondrocytes. The P2Y2 agonists ATP and UTP stimulated a small release of PGE2 that was potentiated after pretreatment with rHuIL-1alpha. PGE2 release in response to ATP and UTP cotreatment was not additive, but release in response to coaddition of ATP and bradykinin (BK) or UTP and BK was additive, consistent with ATP and UTP competition for the same receptor site. The potentiation of PGE2 release in response to ATP and UTP after rHuIL-1alpha pretreatment was mimicked by phorbol myristate acetate. CONCLUSION: Human chondrocytes express both P1 and P2 purine receptor subtypes. The function of the P1 receptor subtype is not yet known, but stimulation of the P2Y2 receptor increases IL-1-mediated PGE2 release.  (+info)

Molecular cloning of mouse and bovine chondromodulin-II cDNAs and the growth-promoting actions of bovine recombinant protein. (4/3820)

We previously determined the complete primary sequence of a heparin-binding growth-promoting factor, chondromodulin-II (ChM-II), which stimulated the growth of chondrocytes and osteoblasts in culture. Bovine ChM-II was a 16-kDa basic protein with 133 amino acid residues and exhibited a significant sequence similarity to the repeats of the chicken mim-1 gene product. Here we report the nucleotide sequences of bovine and mouse ChM-II cDNAs. The cDNAs each contained an open-reading frame corresponding to the ChM-II precursor with 151 amino acid residues. The N-terminus of the precursor included a secretory signal sequence of 18 amino acids prior to the mature ChM-II sequence. Unlike MIM-1, there was no repeat structure in the precursor protein, indicating that ChM-II was encoded as a gene product distinct from MIM-1. We then expressed recombinant bovine ChM-II protein which was purified to homogeneity. The recombinant protein stimulated the growth of rabbit growth plate chondrocytes, mouse MC3T3-E1 cells and rat UMR-106 osteoblastic cells in vitro.  (+info)

Gene transfer of cytokine inhibitors into human synovial fibroblasts in the SCID mouse model. (5/3820)

OBJECTIVE: To investigate the effects of retrovirus-based gene delivery of inhibitory cytokines and cytokine inhibitors into human synovial fibroblasts in the SCID mouse model of rheumatoid arthritis (RA). METHODS: The MFG vector was used for gene delivery of tumor necrosis factor alpha receptor (TNFalphaR) p55, viral interleukin-10 (IL-10), and murine IL-10 into RA synovial fibroblasts. The effect on invasion of these cells into human articular cartilage and on perichondrocytic cartilage degradation was examined after 60 days of coimplantation into the SCID mouse. RESULTS: TNFalphaR p55 gene transfer showed only a limited effect on inhibition of RA synovial fibroblast invasiveness and cartilage degradation. In contrast, invasion of the RA synovial fibroblasts into the coimplanted cartilage was strongly inhibited by both viral and murine IL-10. Perichondrocytic cartilage degradation was not affected by either form of IL-10. CONCLUSION: The data show that cytokines can be successfully inserted into the genome of human RA synovial fibroblasts using a retroviral vector delivery system, and that the SCID mouse model of human RA is a valuable tool for examining the effects of gene transfer. In addition, inhibition of more than one cytokine pathway may be required to inhibit both synovial- and chondrocyte-mediated cartilage destruction in RA.  (+info)

Transduction mechanisms of porcine chondrocyte inorganic pyrophosphate elaboration. (6/3820)

OBJECTIVE: To investigate cellular signaling mechanisms that influence chondrocyte production of inorganic pyrophosphate (PPi), which promotes calcium pyrophosphate dihydrate (CPPD) crystal deposition. METHODS: Articular chondrocyte and cartilage cultures were stimulated with protein kinase C (PKC) activator and adenyl cyclase activator. Generation of extracellular PPi was measured. RESULTS: Adenyl cyclase activation resulted in diminished pyrophosphate generation. PKC activation stimulated pyrophosphate elaboration. CONCLUSION: Two signaling pathways, cAMP and PKC, modulate generation of extracellular pyrophosphate by cartilage and chondrocytes. They are novel targets for potentially diminishing extracellular pyrophosphate elaboration that leads to CPPD crystal deposition.  (+info)

COL9A3: A third locus for multiple epiphyseal dysplasia. (7/3820)

Multiple epiphyseal dysplasia (MED), an autosomal dominant osteochondrodysplasia, is a clinically and genetically heterogeneous disorder characterized by mild short stature and early-onset osteoarthritis. The phenotypic spectrum includes the mild Ribbing type, the more severe Fairbank type, and some unclassified forms. Linkage studies have identified two loci for MED. One of these, EDM1, is on chromosome 19, in a region that contains the cartilage oligomeric matrix protein (COMP) gene. Mutations have been identified in this gene in patients with the Ribbing type, the Fairbank type, and unclassified forms of MED. The second locus, EDM2, maps to chromosome 1, in a region spanning COL9A2. Recently, a splice-site mutation was found in COL9A2, causing skipping of exon 3 in one family with MED. Because of the exclusion of the EDM1 and EDM2 loci in some families, the existence of a third locus has been postulated. We report here one family with MED, evaluated clinically and radiologically and tested for linkage with candidate genes, including COMP, COL9A1, COL9A2, and COL9A3. No linkage was found with COMP, COL9A1, or COL9A2, but an inheritance pattern consistent with linkage was observed with COL9A3. Mutation analysis of COL9A3 identified an A-->T transversion in the acceptor splice site of intron 2 in affected family members. The mutation led to skipping of exon 3 and an in-frame deletion of 12 amino acid residues in the COL3 domain of the alpha3(IX) chain and thus appeared to be similar to that reported for COL9A2. This is the first disease-causing mutation identified in COL9A3. Our results also show that COL9A3, located on chromosome 20, is a third locus for MED.  (+info)

Multilineage potential of adult human mesenchymal stem cells. (8/3820)

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.  (+info)

In order to be able to use second-generation ACT techniques for the repair of cartilage defects in patients with OA, it is highly important to investigate whether OA chondrocytes have an irreversibly altered phenotype or if these cells can differentiate towards a hyaline cartilage phenotype after in vitro expansion. Today, there are conflicting data whether OA chondrocytes fulfill the prerequisites for ACT treatment or not [12, 13, 15, 21]. This encouraged us to investigate more thoroughly the chondrogenic differentiation potential of human OA chondrocytes using microarray technology in order to determine whether OA chondrocytes might possibly be used in second-generation ACT.. Microarray analysis of human OA and ND chondrocytes cultured in ML indicated that the OA chondrocytes were in a less differentiated state compared with the ND chondrocytes. This is thus in accordance with the differences detected in vivo between OA and ND cartilage [10, 22]. Re-differentiation in scaffold cultures ...
Objective: To use deep sequencing to identify novel microRNAs in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate microRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. Results: We identified 990 known microRNAs and 1621 potential novel microRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate microRNAs were analysed further, of which 6 remained after northern blot ...
Aigner, Thomas, Gebhard, Pia Margarethe, Schmid, Erik, Bau, Brigitte, Harley, Vincent and Poschl, Ernst (2003) SOX9 expression does not correlate with type II collagen expression in adult articular chondrocytes. Matrix Biology, 22 (4). pp. 363-372. ISSN 1569-1802 Full text not available from this repository. (Request a copy ...
The aim of the present study was to investigate the effects of phosphorylated osteopontin (p-OPN) on apoptosis and pro-inflammatory cytokine expression in human knee osteoarthritis (OA) chondrocytes. Human knee OA chondrocytes obtained from patients who underwent total knee arthroplasty were treated with p‑OPN, OPN or buffer. Reverse transcription quantitative‑polymerase chain reaction (RT‑qPCR) and western blot analysis were used to assess the expression levels of proinflammatory factors, including interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑6 and nuclear factor (NF)‑κB. Apoptosis of human knee OA chondrocytes was detected by Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometry. Compared with the controls, chondrocytes treated with OPN exhibited higher mRNA and protein expression levels of proinflammatory factors (IL‑1β, TNF‑α, IL‑6 and NF‑κB), and a higher percentage of apoptotic chondrocytes. Furthermore, chondrocytes treated with p‑OPN ...
Background: Recent studies have provided evidence that integrins play roles in recognition of mechanical stimuli and its translation into a cellular response. Integrin signaling may be regulated by a number of mechanisms including accessory proteins such as CD98 (4F2 antigen). Objectives: To determine CD98 expression by human articular chondrocytes and its involvement in human articular mechanotransduction. Methods: CD98 expression was assessed by immunostaining of cryostat sections of snap frozen articular cartilage and in cultured cells by western blotting. Chondrocytes enzymatically isolated from macroscopically normal and osteoarthritic (OA) articular cartilage were grown in short term, primary monolayer culture and used in a resting state or following mechanical stimulation at 0.33Hz. Results: Human articular chondrocytes express CD98 and immunoreactivity revealed a similar heterogeneous pattern of CD98 in both normal and osteoarthritic (OA) human articular cartilage. No role of CD98 was detected
TY - JOUR. T1 - Expression and regulation of Toll-like receptor 2 by IL-1β and fibronectin fragments in human articular chondrocytes. AU - Su, S. L.. AU - Tsai, C. D.. AU - Lee, C. H.. AU - Salter, D. M.. AU - Lee, Herng Sheng. PY - 2005/10. Y1 - 2005/10. N2 - Objective: The objective of this study was to examine expression and regulation of Toll-like receptor 2 (TLR2) in human articular chondrocytes. Methods: Human articular chondrocytes were enzymatically isolated from normal and osteoarthritic knee cartilage. Immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the expression of toll-like receptors. Following stimulation of chondrocytes in vitro by IL-1β and fibronectin proteolytic fragments, the relative levels of mRNA for TLR2 were determined by quantitative real-time PCR. MyD88 activation and nuclear factor-κB (NF-κB) translocation were evaluated by immunoprecipitation and electrophoretic mobility shift assay, ...
TY - JOUR. T1 - Evaluation of the post-treatment anti-inflammatory capacity of osteoarthritic chondrocytes. T2 - An in vitro study using baicalein. AU - Wu, Chang Chin. AU - Chen, Yi Ru. AU - Lu, Dai Hua. AU - Hsu, Li Ho. AU - Yang, Kai Chiang. AU - Sumi, Shoichiro. PY - 2020/6. Y1 - 2020/6. N2 - Introduction: Targeting inflammatory cascades is considered a promising way to prevent knee osteoarthritis (OA) progression. In terms of down-regulating the expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and matrix metalloproteinases (MMPs), pre-treatment with the flavonoid baicalein reportedly protects articular chondrocytes against the cytotoxicity of IL-1β. However, the benefits of post-treatment baicalein on osteoarthritic chondrocytes are not fully elucidated. Methods: In this study, primary human chondrocytes were stimulated with IL-1β prior to baicalein application to evaluate the therapeutic effect of post-treatment. Results: Post-treatment baicalein alleviated cell ...
Osteoarthritis (OA), a non-inflammatory, degenerative disease of articular cartilages, is a common cause of poor performance and early retirement in equine athletes. Pathologically, OA is characterized by matrix degradation and decreased chondrocyte numbers. A mechanical stress is believed to be the major etiologic factor of OA development. Recent studies have indicated that apoptosis is responsible for hypocellularity in OA cartilage and that chondrocyte death by apoptosis could directly contribute to matrix degradation. Increased nitric oxide (NO), a free radical, has been implicated as a cause of chondrocyte apoptosis. No studies, however, have been performed on chondrocyte apoptosis in equine OA. We investigated chondrocyte apoptosis in equine OA cartilage and its relationship to matrix degradation and NO production. Furthermore, we studied whether mechanical stress could induce chondrocyte apoptosis and how NO production and Bcl-2 and caspase-3 proteins contribute to chondrocyte apoptosis by using
Fingerprint Dive into the research topics of Culture surfaces coated with various implant materials affect chondrocyte growth and metabolism. Together they form a unique fingerprint. ...
Background/Purpose: Osteoarthritis (OA) is the most common form of arthritis, affecting nearly 10% of the US population. With age and injury, chondrocytes have diminished mitochondrial content and mitochondrial production of ATP contributing to OA pathogenesis. We have previously reported that chondrocytes release ATP, which is converted extracellularly to adenosine and maintains chondrocyte homeostasis via endogenous stimulation of the A2AR. Injured/inflamed chondrocytes have lower ATP levels and release less ATP resulting in diminished extracellular adenosine and A2AR stimulation. Mice and humans lacking the capacity to convert extracellular ATP to adenosine (ecto-5nucleotidase deficient) develop spontaneous OA as do mice lacking A2AR (A2ARKO). We therefore studied the effect of A2AR stimulation on mitochondrial health and function in chondrocytes from WT and A2ARKO mice and in a human chondrocytic cell line. Methods: A human chondrocyte cell line, T/C28-a2, or neonatal chondrocytes isolated ...
TY - JOUR. T1 - Molecular phenotyping of HCS-2/8 cells as an in vitro model of human chondrocytes. AU - Saas, J.. AU - Lindauer, K.. AU - Bau, B.. AU - Takigawa, M.. AU - Aigner, Thomas. N1 - Funding Information: Funding sources: This work was supported by the BMBF (grant 01GG9824) and Aventis Pharma Deutschland GmbH. Funding Information: This work was supported by the BMBF (grant 01GG9824) and Aventis Pharma Deutschland GmbH. We are grateful to Drs M.B. Goldring (Boston) and J. Block (Chicago) for the chondrocyte cell lines C28I2 and C28a4 as well as AG and SG. The SW1353 chondrosarcoma cell line was obtained by ATCC (Manassas, Virginia, USA).. PY - 2004/11. Y1 - 2004/11. N2 - Objective: Cultures of primary articular chondrocytes for studying chondrocyte biology are notoriously difficult to handle. One alternative is the use of chondrocytic cell lines. Because the HCS-2/8 cells are the most widely used cell line in cartilage research, we investigated the molecular phenotype of these cells by ...
The PI3K pathway has been shown to affect numerous cellular processes in a tissue-specific fashion; for example, it is required for survival in different cell types such as cardiomyocytes [34], cellular differentiation in the case of osteoclasts and keratinocytes [35, 36], and proliferation and differentiation of osteoblasts [35]. It also stimulates differentiation of CD4+ T-cells [37] and development and proliferation of B cells [38, 39]. We hypothesized that the PI3K pathway has similar effects in the growth plate, promoting endochondral bone growth by increasing proliferation and differentiation of chondrocytes and by suppressing apoptosis.. We found that inhibition of PI3K with LY294002 results in decreased differentiation, in both primary chondrocytes (micromass cultures) and organ cultures. Markers of both early chondrocyte differentiation such as collagen II and glycosaminoglycans and of late hypertrophic differentiation such as collagen X, p57, Alkaline phosphatase activity and calcium ...
A number of previous studies have reported that carvacrol possesses anti-inflammatory effects (24-27). Results from the present study indicated that carvacrol inhibited NO and PGE2 production, as well as decreased iNOS and COX-2 expression. Carvacrol was also demonstrated to suppress the protein expression levels of MMP-3 and MMP-13 in IL-1β-stimulated human OA chondrocytes. Furthermore, carvacrol suppressed the activation of NF-κB signaling pathway in IL-1β-induced human chondrocytes.. IL-1β treatment has been widely used to mimic the microenvironment of OA in in vitro studies (28-30); in the present study, IL-1β-induced human OA chondrocytes were used as a model to investigate the protective effects of carvacrol on human chondrocytes, and the results suggested that pretreatment with carvacrol was able to reverse IL-1β-reduced cell viability.. NO has been demonstrated to serve a pivotal role in the development of OA (31). It is produced by iNOS in several types of cells, including ...
Mechanical overloading of cartilage producing hydrostatic stress, tensile strain, and fluid flow can adversely affect chondrocyte function and precipitate osteoarthritis (OA). Application of high fluid shear stress to chondrocytes recapitulates the earmarks of OA, as evidenced by the release of pro-inflammatory mediators, matrix degradation, and chondrocyte apoptosis. Elevated levels of cyclooxygenase-2 (COX-2), prostaglandin (PG) E2, and interleukin (IL)-6 have been reported in OA cartilage in vivo, and in shear-activated chondrocytes in vitro. Although PGE2 positively regulates IL-6 synthesis in chondrocytes, the underlying signaling pathway of shear-induced IL-6 expression remains unknown. Using the human T/C-28a2 chondrocyte cell line as a model system, we demonstrate that COX-2-derived PGE2 signals via up-regulation of E prostanoid (EP) 2 and down-regulation of EP3 receptors to raise intracellular cAMP, and activate protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3-K)/ Akt pathways. PKA
Intercalation movement of proliferative chondrocytes is crucial for their columnar organization which is essential for proper function of growth plate cartilage. The conventional motor protein kinesin‐1 directionally transporting various cargos along microtubules might be involved in this polarized cell movement. Kinesin‐1 is suggested to transport unknown cargo(s) modulating focal adhesion (FA) turnover which is a key step in cell movement. To investigate kinesin‐1s role in chondrocytes intercalation, we generate kinesin‐1 heavy chain (Kif5b) knockout mouse. In the growth plate of KIF5B deficient mouse, we observed abnormal cell morphology and disrupted columnar structure. Isolated mutant chondrocytes show reduced motility and adhesion ability to ECM proteins. Vinculin, the key regulator of focal adhesions, is found as a potential protein associated with KIF5B in mouse chondrocytes. Further study will investigate whether KIF5B affects chondrocytes motility and adhesion via FAs ...
TY - JOUR. T1 - Nitric oxide-nitric oxide synthase regulates key maturational events during chondrocyte terminal differentiation. AU - Teixeira, Cristina C.. AU - Ischiropoulos, Harry. AU - Leboy, Phoebe S.. AU - Adams, Sherrill L.. AU - Shapiro, Irving M.. PY - 2005/7. Y1 - 2005/7. N2 - The goal of this investigation was to explore the mechanism by which NOS and NO serve to regulate events linked to chondrocyte terminal differentiation. NOS isoform expression and NO adducts in chick growth cartilage were detected by immunohistochemistry and Western blot analysis. All NOS isoforms were expressed in chick growth plate chondrocytes with the highest levels present in the hypertrophic region. The enzymes were active since nitrosocysteine and nitrotyrosine residues were detected in regions of the epiphysis with the highest levels of NOS expression. Maturing chick sternal chondrocytes evidenced an increase in NO release and a rise in NOS protein levels. When treated with NOS inhibitors, there was a ...
Osteoarthritis (OA) is a debilitating disease of the joints characterized by cartilage degradation but to date there is no available pharmacological treatment to inhibit disease progression neither is there any available biomarker to predict its development. In the present study, we examined the expression level and possible involvement of novel cell-ECM adhesion-related molecules such as Iintegrin Linked Kinase (ILK), PINCH, parvin, Mig-2 and Migfilin in OA pathogenesis using primary human articular chondrocytes from healthy individuals and OA patients. Our findings show that only ILK and Migfilin were upregulated in OA compared to the normal chondrocytes. Interestingly, Migfilin silencing in OA chondrocytes rather exacerbated than ameliorated the osteoarthritic phenotype, as it resulted in even higher levels of catabolic and hypertrophic markers while at the same time induced reduction in ECM molecules such as aggrecan. Furthermore, we also provide a link between Migfilin and beta-catenin ...
Hypertrophic chondrocytes contained the highest numerical abundance of peroxisomes compared to proliferative chondrocytes as examples for endochondral ossification.
Osteoarthritis (OA) is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood. We investigated the effects of the CC chemokine eotaxin-1 (CCL11) on the matrix metalloproteinase (MMP) expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes. Eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK) and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3,5-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA) inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression
15-Lipoxygenases and their metabolites have been shown to exhibit anti-inflammatory and immunomodulatory properties, but little is known regarding their expression and function in chondrocytes. The objective of this study was to evaluate the expression of 15-lipoxygenase-1 and -2 in human articular chondrocytes, and to investigate the effects of their metabolites 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids on IL-1β-induced matrix metalloproteinase (MMP)-1 and MMP-13 expression. The expression levels of 15-lipoxygenase-1 and -2 were analyzed by reverse transcription PCR and Western blotting in chondrocytes, and by immunohistochemistry in cartilage. Chondrocytes or cartilage explants were stimulated with IL-1β in the absence or presence of 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids, and the levels of MMP-1 and MMP-13 protein production and type II collagen cleavage were evaluated using immunoassays. The role of peroxisome proliferator-activated
FILGUEIRAS, R.R et al. Effect of freezing on rabbit cultured chondrocytes. Arq. Bras. Med. Vet. Zootec. [online]. 2011, vol.63, n.1, pp.46-55. ISSN 1678-4162. http://dx.doi.org/10.1590/S0102-09352011000100008.. This work evaluated the effect of freezing on chondrocytes maintained in culture, aiming the establishment of a cell bank for future application as heterologous implant. Chondrocytes extracted from joint cartilage of nine healthy New Zealand White rabbits were cultivated and frozen with the cryoprotector 5% dimethylsulfoxide for six months. Phenotypic and scanning electron microscopy analyses were carried out to identify morphological and functional differences between fresh and thawed cells. After enzymatic digestion, a total of 4.8x105cells per rabbit were obtained. Fresh chondrocytes showed a high mitotic rate and abundant matrix was present up to 60 days of culture. Loss of phenotypic stability was notable in the thawed chondrocytes, with a low labeling of proteoglycans and weak ...
During longitudinal development of the long bone cartilage, periarticular chondrocyte differentiation, which adds cells to the columnar region, is followed by chondrocyte hypertrophy, which reduces cells in the columnar region. Therefore, the length of the columnar chondrocyte region is determined by three parameters: the pace of periarticular chondrocyte differentiation, the pace of chondrocyte hypertrophy and the rate of columnar chondrocyte proliferation (Fig. 7). As upregulated Ihh signaling promotes periarticular chondrocyte differentiation and increases the rate of columnar chondrocyte proliferation (Kobayashi et al., 2005b), the proliferating columnar chondrocyte region would be increased if chondrocyte hypertrophy were not altered. Our observation that the columnar chondrocyte region was shorter in the PTHrP-/-;Ptch1c/-; Col2a1-Cre double mutant than in the PTHrP-/- single mutant (Fig. 2B, Fig. 3A) demonstrates that Hh signaling also acts to promote chondrocyte hypertrophy in the absence ...
INTRODUCTION: Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-kappaB signalling pathway. METHODS: We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1beta-stimulated human chondrocytes in vitro using ...
Chondrogenesis occurs via three steps: (a) commitment to chondrocyte differentiation by mesenchymal cells, seen as mesenchymal condensation; (b) chondrocyte proliferation in the growth plate to facilitate longitudinal development; and (c) differentiation of proliferating chondrocytes to hypertrophic chondrocytes (for review see references 1, 2). During endochondral ossification, chondrocyte hypertrophy is critical, because cells alter the extracellular matrix and induce vascular invasion. Extrinsic factors such as bone morphogenetic proteins, Indian hedgehog, and modulators such as Sox9, Runx2, Smads, and histone deacetylase 4 are reportedly essential for chondrogenesis (1, 2). Loss of histone deacetylase 4 causes early onset of hypertrophy, followed by growth retardation (6). Overexpression of Runx2 under the control of a type II collagen promoter/enhancer induces dwarfism because of precocious endochondral ossification and accelerated chondrocyte differentiation (4, 5). Thus, regulation of ...
Mechanical forces can stimulate the production of extracellular matrix molecules. We tested the efficacy of ultrasound to increase proteoglycan synthesis in bovine primary chondrocytes. The ultrasound-induced temperature rise was measured and its contribution to the synthesis was investigated using bare heat stimulus. Chondrocytes from five cellular isolations were exposed in triplicate to ultrasound (1 MHz, duty cycle 20%, pulse repetition frequency 1 kHz) at average intensity of 580 mW/cm2 for 10 minutes daily for 1-5 days. Temperature evolution was recorded during the sonication and corresponding temperature history was created using a controllable water bath. This exposure profile was used in 10-minute-long heat treatments of chondrocytes. Heat shock protein 70 (Hsp70) levels after one-time treatment to ultrasound and heat was analyzed by Western blotting, and proteoglycan synthesis was evaluated by 35S-sulfate incorporation. Ultrasound treatment did not induce Hsp70, while heat treatment ...
TY - JOUR. T1 - Can microcarrier-expanded chondrocytes synthesize cartilaginous tissue in vitro?. AU - Surrao, Denver C. AU - Khan, Aasma A. AU - McGregor, Aaron J. AU - Amsden, Brian G. AU - Waldman, Stephen D. PY - 2011/8. Y1 - 2011/8. N2 - Tissue engineering is a promising approach for articular cartilage repair; however, it is challenging to produce adequate amounts of tissue in vitro from the limited number of cells that can be extracted from an individual. Relatively few cell expansion methods exist without the problems of de-differentiation and/or loss of potency. Recently, however, several studies have noted the benefits of three-dimensional (3D) over monolayer expansion, but the ability of 3D expanded chondrocytes to synthesize cartilaginous tissue constructs has not been demonstrated. Thus, the purpose of this study was to compare the properties of engineered cartilage constructs from expanded cells (monolayer and 3D microcarriers) to those developed from primary chondrocytes. Isolated ...
In this study, we used murine chondrocytes as an in vitro model and mice exhibiting destabilization of the medial meniscus (DMM) as an in vivo model to investigate the mechanisms through which S-allyl cysteine (SAC) alleviates osteoarthritis (OA). SAC significantly reduced apoptosis and senescence and maintained homeostasis of extracellular matrix (ECM) metabolism in tert-butyl hydroperoxide (TBHP)-treated chondrocytes. Molecular docking analysis showed a –CDOCKER interaction energy value of 203.76 kcal/mol for interactions between SAC and nuclear factor erythroid 2-related factor 2 (Nrf2). SAC increased the nuclear translocation of Nrf2 and activated the Nrf2/HO1 signaling pathway in TBHP-treated chondrocytes. Furthermore, Nrf2 knockdown abrogated the antiapoptotic, antisenescence, and ECM regulatory effects of SAC in TBHP-treated chondrocytes. SAC treatment also significantly reduced cartilage ossification and erosion, joint-space narrowing, synovial thickening and
In cartilage tissue engineering, hydrogel is widely used as the scaffold for hosting and culturing chondrocyte suspension during neo-tissue formation. In order to develop cultured chondrocytes into a functional cartilage equivalent, the hydrogel must provide an ideal microenvironment for the rapidly proliferating chondrocytes. At the same time, the essential functions of chondrocytes, such as the secretion of type II collagen and glycosaminoglycans, must be maintained. In these studies, we quantitatively characterize the mechanobiology underlying a newly discovered edge flourish phenomenon of cultured chondrocytes within a three-dimensional agarose hydrogel, which may ultimately nurture scaffold-free cartilaginous tissue regeneration. First, real-time microscopy was used to track the spatiotemporal distributions of chondrocytes at different focal planes. The chondrocytes were observed to exhibit abundant neo-tissue outgrowth and significant cartilaginous phenotype at the edge of the hydrogel ...
Transformed chondrocyte cell lines and primary OA human articular chondrocytes (HAC) were grown in monolayer culture. Cells were exposed to cyclical mechanical stimulation (MS) using an apparatus that produces strain on the base of the culture dish, causing the deformation of attached cells. Chondrocytes were also incubated with a cytokine cocktail containing IL-1β, TNFα, IL-6 and IFNγ (CYT). The transformed chondrocyte cell lines C20A4 and C2812 did not express detectable levels of NOS protein or nitrite activity. However increased inducible NOS (iNOS) mRNA following CYT stimulation suggested that the cells were able to sense the CYT stimulation. Primary OA HAC showed increased production of iNOS mRNA, protein and nitrite following CYT or IL-1β stimulation. The simultaneous application of CYT and MS also showed elevated iNOS mRNA, protein and nitrite levels, although these were significantly lower than following CYT alone. An IL-4 neutralising antibody and a β1 integrin function blocking ...
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The mechanical environment of the chondrocyte is an important factor that influences the maintenance of the articular cartilage extracellular matrix. Previous studies have utilized theoretical models of chondrocytes within articular cartilage to predict the stress-strain and fluid flow environments around the cell, but little is currently known regarding the cellular properties which are required for implementation of these models. The objectives of this study were to characterize the mechanical behavior of primary human chondrocytes and to determine the Youngs modulus of chondrocytes from non-osteoarthritic (`normal) and osteoarthritic cartilage. A second goal was to quantify changes in the volume of isolated chondrocytes in response to mechanical deformation. The micropigette aspiration technique was used to measure the deformation of a single chondrocyte into a glass micropipette in response to a prescribed pressure. The results of this study indicate that the human chondrocyte behaves as a ...
Häuselmann HJ, Stefanovic-Racic M, Michel BA, Evans CH. Differences in nitric oxide production by superficial and deep human articular chondrocytes: implications for proteoglycan turnover in inflammatory joint diseases. J Immunol. 1998 Feb 01; 160(3):1444-8 ...
Low density lipoprotein receptor (LDLR)-related protein 1 (LRP1/CD91) is one of the receptors of CCN2 that conducts endochondral ossification and cartilage repair. LRP1 is a well-known endocytic receptor, but its distribution among chondrocytes remains to be elucidated. We herein demonstrate for the first time that the distribution of LRP1 in chondrocytes except for hypertrophic chondrocytes in vivo and in vitro. Interestingly, the LRP1 levels were higher in mature chondrocytic HCS-2/8 and osteoblastic SaOS-2 than in other cells, whereas the other LDLR family members involved in ossification were detected at lower levels in HCS-2/8. It was interesting to note that in HCS-2/8, LRP1 was observed not only on the cell surface and in the cytoplasm, but also in the nucleus. Exogenously added CCN2 was incorporated into HCS-2/8, which was partially co-localized with LRP1, and targeted to the recycling endosomes and nucleus as well as the lysosomes. These findings suggest specific roles of LRP1 in ...
An early event in skeletal joint development is the specification of articular chondrocytes at the joint surface. Articular chondrocytes are distinct in producing lower levels of cartilage matrix and not being replaced by bone, yet how they acquire these properties remains poorly understood. Here, we show that two members of the Iroquois transcriptional repressor family, Irx7 and Irx5a, function to block chondrocyte maturation at the developing hyoid joint of zebrafish. These Irx factors suppress the production of cartilage matrix at the joint in part by preventing the activation of a col2a1a enhancer by Sox9a. Further, both zebrafish Irx7 and mouse IRX1 are able to repress cartilage matrix production in a murine chondrogenic cell line. Iroquois proteins may therefore have a conserved role in keeping chondrocytes in an immature state, with the lower levels of cartilage matrix produced by these immature cells contributing to joint flexibility ...
Chondrocytes produce RANTES and express RANTES receptors. RANTES and CCR5 were markedly increased in OA and after in vitro treatment of normal chondrocytes with IL-1. Chondrocyte activation and cartilage degradation were identified as novel biologic and pathogenetic activities of this chemokine.
Background Donor site morbidity, limited amounts of cells, lack of phenotype during extension, and age-related drop in chondrogenic activity present critical road blocks to the usage of autologous chondrocyte implantation for cartilage fix. neocartilage made by juvenile chondrocytes was 100-flip greater than WHI-P180 in neocartilage made by adult cells. Collagen type type and II IX mRNAs in clean juvenile chondrocytes had been 100- and 700-collapse higher, respectively, than in adult chondrocytes. The distributions of collagens II and IX had been similar in indigenous juvenile cartilage and in neocartilage created by juvenile cells. Juvenile cells grew considerably quicker in monolayer civilizations than adult cells (p = 0.002) and proteoglycan amounts stated in agarose lifestyle was significantly higher in juvenile cells than in adult cells after multiple passages (p < 0.001). Juvenile chondrocytes didnt stimulate lymphocyte proliferation. Conclusions These outcomes record a dramatic age group ...
Carbonic anhydrase (CA) IX is a transmembrane isozyme of CAs that catalyzes reversible hydration of CO(2). CA IX is distributed in human embryonic chondrocytes. Car9 mRNA and CA IX [are] expressed in proliferating but not hypertrophic chondrocytes. Next, we examined the role of CA IX in the expression of marker genes of chondrocyte differentiation in vitro. Introduction of Car9 siRNA to mouse primary chondrocytes obtained from costal cartilage induced the mRNA expressions of Col10a1, the gene for type X collagen α-1 chain, and Epas1, the gene for hypoxia-responsible factor-2α (HIF-2α), both of which are known to be characteristically expressed in hypertrophic chondrocytes. On the other hand, forced expression of CA IX had no effect of the proliferation of chondrocytes or the transcription of Col10a1 and Epas1, while the transcription of Col2a1 and Acan were up-regulated. Although HIF-2α has been reported to be a potent activator of Col10a1 transcription, Epas1 siRNA did not suppress Car9 ...
Both mechanical load and elevated levels of proinflammatory cytokines have been associated with the risk for developing osteoarthritis (OA), yet the potential interaction of these mechanical and biological factors is not well understood. The purpose of this study was to evaluate the response of chondrocytes to the effects of dynamic unconfined compression, TNF-α, and the simultaneous effects of dynamic unconfined compression and TNF-α. The response to these three treatments was markedly different and, taken together, the response in the gene expression of chondrocytes to the different treatment conditions suggest a complex interaction between structure, biology, and mechanical loading.. ...
Cell-to-cell diffusion of second messengers across intercellular channels allows tissues to co-ordinate responses to extracellular stimuli. Intercellular diffusion of inositol 1,4,5-trisphosphate, locally produced by focal stimulations, sustains the propagation of intercellular Ca2+ waves, by stimulating the release of intracellular Ca2+ in neighbouring cells. We previously demonstrated that in cultured articular chondrocytes and HIG-82 synovial cells, studied with digitial fluorescence video imaging, mechanical stimulation of a single cell induced intercellular Ca2+ waves dependent on the presence of gap junctions. In the absence of extracellular Ca2+ the propagating distance of the wave decreased significantly in HIG-82 cells, but appeared unaffected in chondrocytes. We now show that both cells types express connexin 43 and a similar functional coupling, thus suggesting that the different Ca2+ sensitivity of intercellular waves is not due to major differences in gap junction constituent ...
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The various forms of joint loading have been found to differentially influence anatomical and molecular responses, which together are aimed to maintain the joint homeostasis. To elucidate these mechanisms of mechanotransduction, we review the roles of the distinct joint components, as well as numerous in vitro studies that have been performed to ... read more unravel chondrocyte responses in changing environments. The main signalling pathways in transduction of load signals are initiated by integrins sensing matrix deformation and by altered interstitial pH, influencing ion fluxes through membrane channels. Downstream signalling after static compression occurs mainly via the MAPK pathways of ERK1/2, SAPK (Jnk) and p38, which directly influence transcription factors of genes involved in cartilage breakdown. In contrast, cyclic compression and mild shear forces lead to membrane hyperpolarisation and subsequently stimulates cartilage matrix synthesis. These findings add further comprehension with ...
Results Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 µm in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including α-tubulin and β-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L-lysine and L-arginine between chondrocytes.. ...
A great deal of effort has been focused on exploring the underlying molecular mechanism of osteoarthritis (OA) especially at the cellular level. We report a confocal Raman spectroscopic investigation on human osteoarthritic chondrocytes. The objective of this investigation is to identify molecular features and the stage of OA based on the spectral signatures corresponding to bio-molecular changes at the cellular level in chondrocytes. In this study, we isolated chondrocytes from human osteoarthritic cartilage and acquired Raman spectra from single cells. Major spectral differences between the cells obtained from different International Cartilage Repair Society (ICRS) grades of osteoarthritic cartilage were identified. During progression of OA, a decrease in protein content and an increase in cell death were observed from the vibrational spectra. Principal component analysis and subsequent cross-validation was able to associate osteoarthritic chondrocytes to ICRS Grade I, II and III with ...
Lu YC, Evans CH, Grodzinsky AJ. Effects of short-term glucocorticoid treatment on changes in cartilage matrix degradation and chondrocyte gene expression induced by mechanical injury and inflammatory cytokines. Arthritis Res Ther. 2011; 13(5):R142 ...
TY - JOUR. T1 - Expression and production of stathmin in growth plate chondrocytes is cell-maturation dependent. AU - Hummert, Thomas W.. AU - Schwartz, Zvi. AU - Sylvia, Victor L.. AU - Dean, David D.. AU - Hardin, Robert R.. AU - Boyan, Barbara D.. PY - 2000. Y1 - 2000. N2 - Growth plate cartilage is comprised of linear columns of chondrocytes with the least differentiated cells at one end and the terminally differentiated cells at the other end. Rat costochondral chondrocytes can be divided into the resting cell zone (reserve cell zone), which contains relatively immature chondrocytes (RC cells), and the phenotypically more mature prehypertrophic and upper hypertrophic cell zones, which together may be termed the growth zone chondrocytes (GC cells). When grown separately in monolayer culture, they continue to express their zone-specific phenotype, providing a model for assessing cell-maturation-dependent expression of molecules associated with differentiation. Stathmin (also called prosolin, ...
Herein, we review the regulation of differentiation of the growth plate chondrocytes by G-proteins. In connection with this, we summarize the current knowledge regarding each family of G-protein α subunit, specifically, Gα(s), Gα(q/11), Gα(12/13), and Gα(i/o). We discuss different mechanisms involved in chondrocyte differentiation downstream of G-proteins and different G-protein-coupled receptors (GPCRs) activating G-proteins in the epiphyseal chondrocytes. We conclude that among all G-proteins and GPCRs expressed by chondrocytes, Gα(s) has the most important role and prevents premature chondrocyte differentiation. Receptor for parathyroid hormone (PTHR1) appears to be the major activator of Gα(s) in chondrocytes and ablation of either one leads to accelerated chondrocyte differentiation, premature fusion of the postnatal growth plate, and ultimately short stature.
7.1. Insulin-like growth factors (IGF-I & IGF-II). Of the growth factors, those with the most potent effects on growing skeletal tissue are the IGFs, previously known as somatomedins. IGFs are synthesised in the liver and circulate bound to carrier proteins (Froesch et al., 1985). The major factors regulating IGF concentrations in serum are growth hormone, nutritional intake and thyroid hormones, the latter being necessary for growth hormone secretion. The traditional view was that growth hormone acted indirectly on the growth plate via IGF-I, a potent mitogen for growth plate chondrocytes. However, there is increasing evidence that growth hormone has direct effects on the growth plate (Tripper et al., 1989). (This close relationship between circulating IGFs and growth hormone will be discussed in more detail in the chapter covering the hormonal regulation of growth.). In addition to having effects on the growth plate chondrocytes, locally synthesised and circulating IGFs retained in bone matrix ...
Whartons jelly stem cells (WJSCs) are a potential source of transplantable stem cells in cartilage-regenerative strategies, due to their highly proliferative and multilineage differentiation capacity. We hypothesized that a non-direct co-culture system with human articular chondrocytes (hACs) could enhance the potential chondrogenic phenotype of hWJSCs during the expansion phase compared to those expanded in monoculture conditions. Primary hWJSCs were cultured in the bottom of a multiwell plate separated by a porous transwell membrane insert seeded with hACs. No statistically significant differences in hWJSCs duplication number were observed under either of the culture conditions during the expansion phase. hWJSCs under co-culture conditions show upregulations of collagen type I and II, COMP, TGFβ1 and aggrecan, as well as of the main cartilage transcription factor, SOX9, when compared to those cultured in the absence of chondrocytes. Chondrogenic differentiation of hWJSCs, previously expanded ...
The goal of our investigation was to explore the mechanism by which hypoxia regulates growth plate chondrocyte survival. At low O2 tension, chondrocytes were refractory to a staurosporine (i.e., apoptosis-inducing) challenge. To determine whether hypoxic survival was due to the expression of HIF-1, we evaluated the response of HIF silenced cells to staurosporine. Both, silenced cells and control chondrocytes were equally sensitive to the apoptogen challenge. To learn if resistance was mediated by the proteins of the autophagic pathway, we examined the expression of Beclin 1 and LC3. Both proteins were present in the growth plate as well as in N1511 chondrocytes. Moreover, silencing of Beclin 1 resulted in enhanced chondrocyte death. Thus, this gene served to maintain chondrocyte survival activity. Besides serving a cytoprotective role, it is known that autophagy can function in cell death. Accordingly, to ascertain if autophagy might also sensitize cells to apoptosis, we activated autophagy and examined
AUTOLOGOUS CHONDROCYTE TRANSPLANTATION Melanie McNeal, PT, CSCS, CFT for patients of DAVID LINTNER, MD Articular cartilage (AC) provides a resilient surface for friction free movement of joints. It must bear ...
Joints that have degenerated as a result of aging or injury contain dead chondrocytes and damaged cartilage. Some studies have suggested that chondrocyte death precedes cartilage damage, but how the loss of chondrocytes affects cartilage integrity is not clear. In this study, we examined whether chondrocyte death undermines cartilage integrity in aging and injury using a rapid 3D confocal cartilage imaging technique coupled with standard histology. We induced autonomous expression of diphtheria toxin to kill articular surface chondrocytes in mice and determined that chondrocyte death did not lead to cartilage damage. Moreover, cartilage damage after surgical destabilization of the medial meniscus of the knee was increased in mice with intact chondrocytes compared with animals whose chondrocytes had been killed, suggesting that chondrocyte death does not drive cartilage damage in response to injury. These data imply that chondrocyte catabolism, not death, contributes to articular cartilage damage ...
Autologous chondrocyte implantation (ACI) has been used over the last two decades to treat focal cartilage lesions aiming to delay or prevent the onset of osteoarthritis; however, some patients do not respond adequately to the procedure. A number of biomarkers that can forecast the clinical potency of the cells have been proposed, but evidence for the relationship between in vitro chondrogenic potential and clinical outcomes is missing. In this study, we explored if the ability of cells to make cartilage in vitro correlates with ACI clinical outcomes. Additionally, we evaluated previously proposed chondrogenic biomarkers and searched for new biomarkers in the chondrocyte proteome capable of predicting clinical success or failure after ACI. The chondrogenic capacity of chondrocytes derived from 14 different donors was defined based on proteoglycans staining and visual histological grading of tissues generated using the pellet culture system. A Lysholm score of 65 two years post-ACI was used as a cut-off
The effects of increased hydrostatic pressure on Na+ x H+ exchange activity in bovine articular chondrocytes have been characterized. Chondrocytes were isolated from the cartilage matrix and the cells were loaded with the pH-sensitive fluorophore BCECF. Cells were acidified by ammonium rebound and the rate of recovery of pHi back to control levels was determined using cuvette fluorimetry. The application of hydrostatic pressure (1-300 atm) to cells within the fluorimeter was found to stimulate the rate of recovery from acidification, recorded as proton fluxes, in MOPS buffered media. This increase was dependent on the presence of extracellular Na+ ions and was inhibited by the Na+ x H+ exchange inhibitor EIPA. The pressure-stimulated increase in H+ flux is therefore mediated completely by Na+ x H+ exchange. In addition, the stimulation could be abolished by the kinase inhibitor staurosporine, was not additive with the stimulation of Na+ x H+ exchange elicited by the addition of serum and was unaffected
OBJECTIVE: During joint loading, chondrocytes in the articular cartilage are subjected to gradients of high compressive hydrostatic pressure (HP). In response to diverse chemical or physical stresses, heat shock genes are induced to express heat shock proteins (Hsps). This study sought to examine the role of Hsps in baroresistance in primary bovine chondrocytes and synovial cells, as well as in primary human fibroblasts.. METHODS: Northern blotting was used to analyze the steady-state levels of hsp70 mRNA in the primary cells exposed to HP or heat stress. Hsp70 protein accumulation was analyzed by Western blotting, and the DNA-binding activity was examined by gel mobility shift assay.. RESULTS: Primary bovine chondrocytes which have been adapted to live under pressurized conditions showed negligible Hsp70 response upon HP loading, whereas primary bovine synovial cells and human fibroblasts accumulated hsp70 mRNA and protein when subjected to HP. The response was initiated without activation of ...
Primary Human Chondrocytes (HCH) are isolated from normal human articular cartilage from the knee and hip joints (lot specific source information is available on request). PromoCell HCH are routinely tested for their capacity to differentiate in 3D spheroids.. The articular cartilage covers the joints between bones and contains no blood vessels, lymphatic vessels, or nerve fibers. It is composed of only one specialized cell type, the chondrocytes, which produce and maintain the extracellular matrix of cartilage, i.e. collagen (mostly type II) and proteoglycans (primarily aggrecan).. NEW: Our HCH are now also available from HLA-typed donors.. Available formats:. ...
Recent studies of OA cartilage have identified both messenger RNA (mRNA) and the protein for specific MMPs as well as a collagenase mediated type II collagen degradation product, suggesting that MMPs contribute to the intrinsic chondrocyte mediated degenerative changes of the cartilage matrix in OA.8,12,13 As yet the factors responsible for their expression remain uncertain, although the proinflammatory cytokines interleukin 1 (IL1) and tumour necrosis factor α (TNFα) have been implicated.1,8 The increased levels of histamine found in OA synovial fluids3 have suggested a role for this mediator in the pathophysiology of this disease. Evidence presented here shows that histamine up regulates both MMP-13 and MMP-3 production by chondrocytes. Both these MMPs are important in the degradation of articular cartilage; MMP-13 can degrade collagen type II, and MMP-3 can degrade proteoglycan and collagen types IX and XI, and activate procollagenase-1.14 Earlier studies have shown that chondrocytes ...
Glucose transport across the chondrocyte membrane is essential for chondrogenesis and the development of the skeletal system. We have previously used RT-PCR to show that fully developed human articular chondrocytes express transcripts for the GLUT1 and GLUT9 glucose transporters. In this study we report on the expression and immunohistochemical localization of the GLUT1 and GLUT9 proteins in embryonic and mature ovine cartilage. We also provide Western blot evidence for GLUT1 and GLUT9 expression in mature ovine chondrocytes. Ovine embryos (developmental stages E32 to E36 and E42 to E45) were obtained from pregnant ewes humanely killed by injection with sodium pentobarbitone. Embryos were fixed and processed for immunohistochemistry. Polyclonal antibodies to GLUT1 and GLUT9 revealed that both transporters are expressed in developing chondrocytes in ovine embryos and in the superficial, middle and deep layers of ovine cartilage from mature animals. GLUT1 expression was observed in erythrocytes ...
Tissue engineering-based therapies targeting cartilage diseases, such as osteoarthritis, require in vitro expansion of articular chondrocytes. A major obstacle for these therapies is the dedifferentiation and loss of phenotype accompanying chondrocyte expansion. Recent studies suggest that manipulation of hedgehog signalling may be used to promote chondrocyte re-differentiation. Hedgehog signalling requires the primary cilium, a microtubule-based signalling compartment, the integrity of which is linked to the cytoskeleton. We tested the hypothesis that alterations in cilia expression occurred as consequence of chondrocyte dedifferentiation and influenced hedgehog responsiveness. In vitro chondrocyte expansion to passage 5 (P5) was associated with increased actin stress fibre formation, dedifferentiation and progressive loss of primary cilia, compared to primary (P0) cells. P5 chondrocytes exhibited ~50 % fewer cilia with a reduced mean length. Cilia loss was associated with disruption of ligand-induced
Objective: Oxidative stress occurs when the metabolic balance of a cell is disrupted through exposure to excess pro-oxidant. Whilst it is known that unregulated production or exposure to exogenous sources of pro-oxidants induces chondrocyte cell death and degrades matrix components in vitro, relatively little is known of the effects of pro-oxidants on articular cartilage in situ. The objective of this study was to determine if a single exposure to the pro-oxidant hydrogen peroxide (H2O2) induces a degenerative phenotype. Methods: Articular cartilage explants were obtained from skeletally mature bovine steers and exposed to a single dose of hydrogen peroxide (0.1-1.0 mM) and cultured for up to 21 days. Cell death, and sulfated glycosaminoglycan loss into the medium and gene expression were quantitatively determined. Adoption of an abnormal chondrocyte phenotype was analyzed through the expression of 3B3(−), nitrotyrosine and procollagen type IIA epitopes in cartilage explants. Results: Cell ...
The maintenance and expansion of the cells required for formation of tissue-engineered cartilage has, to date, proven difficult. This is, in part, due to the initial solid phase extracellular matrix demanded by the cells inhabiting this avascular tissue. Herein, we engineer an innovative alginate-fibronectin microfluidic-based carrier construct (termed a chondrobag) equipped with solid phase presentation of growth factors that support skeletal stem cell chondrogenic differentiation while preserving human articular chondrocyte phenotype. Results demonstrate biocompatibility, cell viability, proliferation and tissue-specific differentiation for chondrogenic markers SOX9, COL2A1 and ACAN. Modulation of chondrogenic cell hypertrophy, following culture within chondrobags loaded with TGF-β1, was confirmed by down-regulation of hypertrophic genes COL10A1 and MMP13. MicroRNAs involved in the chondrogenesis process, including miR-140, miR-146b and miR-138 were observed. Results demonstrate the ...
Search and download thousands of Swedish university dissertations (essays). Full text. Free. Dissertation: Production of neocartilage tissues using primary chondrocytes .
Fukai, A.; Kamekura, S.; Chikazu, D.; Nakagawa, T.; Hirata, M.; Saito, T.; Hosaka, Y.; Ikeda, T.; Nakamura, K.; Chung, U-il.; Kawaguchi, H., 2012: Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice
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Chicken vertebral chondrocytes, which normally grow in suspension, synthesize large amounts of cartilage extracellular matrix proteins, but little fibronectin. We have analyzed the effects of both substrate attachment and transformation with a temperature-sensitive mutant of Rous sarcoma virus on fibronectin gene expression in these cells. Our experiments show that viral transformation increases fibronectin synthesis to a greater extent than substrate attachment. Furthermore, transformed chondrocytes have lost the ability to decrease fibronectin synthesis in response to suspension culture, suggesting that transformation alters the normal attachment-responsive control of fibronectin gene expression. Finally, infected substrate-attached chondrocytes shifted to the nonpermissive temperature for transformation use fibronectin RNA more efficiently in protein synthesis than cells grown under the other conditions, suggesting for the first time a role for translational control of fibronectin gene ...
OBJECTIVE: To examine the effect of O(2) and the role, and source, of reactive oxygen species (ROS) on pH regulation in articular chondrocytes. METHODS: Cartilage from equine metacarpo/tarsophalangeal joints was digested (collagenase) to isolate chondrocytes and loaded with 2,7-bis-2-(carboxyethyl)-5(6)-carboxylfluorescein, a pH-sensitive fluorophore. O(2) tension was maintained using Eschweiler tonometers and a Wosthoff gas mixer. Cells were exposed to agents which alter ROS levels, mitochondrial inhibitors and/or inhibitors of protein phosphorylation. ROS levels were determined by dichlorofluorescein and mitochondrial membrane potential measured using JC-1. RESULTS: pH homeostasis was dependent on ROS. Na(+)/H(+) exchanger (NHE) activity was inhibited at low O(2) tension (acid efflux reducing from 2.30+/-0.05 to 1.27+/-0.11mMmin(-1) at 1%). NHE activity correlated with ROS levels (r(2)=0.65). ROS levels were increased by antimycin A (with levels at 1% O(2) tension increasing from 59+/-9% of the
GH has physiological functions in many tissues, but the cellular targets for direct effects of GH remain ill defined in complex tissues such as the growth plate in which the contribution of direct vs. indirect actions of GH remains controversial. The Janus kinase (Jak)-signal transducer and activator of transcription (STAT)-5 pathway is activated by GH, so we developed a method to visualize nuclear Stat5b and phosphorylated Stat5 in single cells in response to a pulse of GH. Hep2 cells did not show a Stat5 phosphorylation (pY-Stat5) response to GH except in cells transfected to express GH receptors. ATDC5 cells express GH receptors and showed GH-induced pY-Stat5 responses, which varied with their state of chondrocyte differentiation. In vivo, Stat5b+ve nuclei were seen in the resting and prehypertrophic chondrocytes of the growth plate. After a single ip pulse of human GH or mouse GH, but not prolactin, pY-Stat5 responses were visible in cells in the resting zone and groove of Ranvier, 10-45 min ...
TY - JOUR. T1 - CCN2 as a novel molecule supporting energy metabolism of chondrocytes. AU - Maeda-Uematsu, Aya. AU - Kubota, Satoshi. AU - Kawaki, Harumi. AU - Kawata, Kazumi. AU - Miyake, Yoshiaki. AU - Hattori, Takako. AU - Nishida, Takashi. AU - Moritani, Norifumi. AU - Lyons, Karen M.. AU - Iida, Seiji. AU - Takigawa, Masaharu. PY - 2014/5. Y1 - 2014/5. N2 - CCN2/connective tissue growth factor (CTGF) is a unique molecule that promotes both chondrocytic differentiation and proliferation through its matricellular interaction with a number of extracellular biomolecules. This apparently contradictory functional property of CCN2 suggests its certain role in basic cellular activities such as energy metabolism, which is required for both proliferation and differentiation. Comparative metabolomic analysis of costal chondrocytes isolated from wild-type and Ccn2-null mice revealed overall impaired metabolism in the latter. Among the numerous metabolites analyzed, stable reduction in the intracellular ...
A multitude of signalling cascades are implicated in the homeostasis of articular chondrocytes. However, the identity of these signalling pathways is not fully established. The 3, 5-cyclic AMP-mediated signalling system is considered to be a prototype. Adenylyl cyclase (AC) is an effector enzyme responsible for the synthesis of cAMP. There are 10 mammalian AC isoforms and some of these are differentially regulated by calcium/calmodulin (Ca2+/CaM). Ca2+ is known to play an important role in the development and maintenance of skeletal tissues. Ca2+/CaM-dependent AC isoforms and their temporal expression in articular chondrocytes in rats were identified using RT-PCR and immunohistochemistry techniques. All Ca2+/CaM-dependent AC isoforms were expressed in chondrocytes from all age groups examined. Each isoform was differentially expressed in developing and adult articular chondrocytes. Generally, expression of AC isoforms was observed to increase with age, but the increase was not uniform for all Ca2+/CaM
Chondrocytes in articular cartilage normally exhibit high expression of collagen II and aggrecan but rapidly dedifferentiate to a fibroblastic phenotype if passaged in culture. Previous studies have suggested that the loss of chondrocyte phenotype is associated with changes in the structure of the F-actin cytoskeleton, which also controls cell mechanical properties. In this study, we examined how dedifferentiation in monolayer influences the mechanical properties of chondrocytes isolated from different zones of articular cartilage. Atomic force microscopy was used to measure the mechanical properties of superficial and middle/deep zone chondrocytes as they underwent serial passaging and subsequent growth on fibronectin-coated, micropatterned self-assembled monolayers that restored a rounded cell shape in 2D culture. Chondrocytes exhibited significant increases in elastic and viscoelastic moduli with dedifferentiation in culture. These changes were only partially ameliorated by the restoration of ...
Here, we elucidated molecular functions of ITGBL1 in cartilage formation and OA development. Itgbl1 is transiently and specifically expressed in developing chondrocytes and promotes chondrogenesis. Our data suggest that ITGBL1 inhibits integrin signaling in developing chondrocytes. Developing chondrocytes constantly contact and interact with the surrounding ECM, and the major receptors for the ECM are integrins. Integrin-ECM interaction was shown to be necessary and to positively regulate prechondrocyte condensation (12-15), whereas other studies reported conflicting data about the functions of integrins in chondrogenic differentiation (17-19). Integrin-ECM interactions promote osteogenic differentiation while inhibiting chondrogenesis in mesenchymal stem cells (17). Increased FAK activation prevents chondrogenesis (39), and intrinsic FAK expression is actively down-regulated in developing chondrocytes (59), which we also confirmed in chondrogenic hBMSCs (fig. S6A). Furthermore, increased ...
Supplementary Materials Supplemental Data supp_5_6_733__index. the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed comparable phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage Sodium Tauroursodeoxycholate formation both in vitro and in vivo and in fixing large knee cartilage defects (6C13 cm2) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and ...
Molecular Mechanisms of Lead in Chondrocyte Differentiation and Skeletal Development. Our research is part of a comprehensive cartilage cell and molecular biology program designed to identify the intracellular signals and pathways important in chondrocyte differentiation. Lead is one of the most important environmental toxicants and we have found that this ion has specific effects on important intracellular signaling pathways in chondrocytes. The work is conducted in the Center for Musculoskeletal Research, which is one of the six Aab Institutes for Biological Sciences, areas of special research focus at this university.. Long bone growth depends on an ordered sequence of maturational changes by growth plate chondrocytes. The changes include large increases in cellular volume, alkaline phosphatase activity, and alterations in matrix synthesis. The differentiation process is regulated by a complex interaction between several important local growth factors, including PTHrP, bone morphogenetic ...
Degradable polymers with a tailorable degradation rate might be promising candidate materials for biomaterial-based cartilage repair. In view of the poor intrinsic healing capability of cartilage, implantation of autologous chondrocytes seeded on a biocompatible slow degrading polymer might be an encouraging approach to improve cartilage repair in the future. This study was undertaken to test if the fiber orientation (random versus aligned) of two different degradable polymers and a polymer intended for long term applications could influence primary articular chondrocytes growth and ultrastructure. A degradable copoly(ether) esterurethane (PDC) was synthesized via co-condensation of poly(p-dioxanone) diol and poly(epsilon-caprolactone) diol using an aliphatic diisocyanate as linker. Poly(p-dioxanone) (PPDO) was applied as commercially available degradable polymer, while polyetherimide (PEI) was chosen as biomaterial enabling surface functionalization. The fibrous scaffolds of PDC and PPDO were ...
Much of the vertebrate skeleton arises from a cartilage template, which subsequently undergoes endochondral bone formation (Erlebacher et al., 1995; Hinchcliffe and Johnson, 1990). At the earliest stage of this process, mesenchymal cells condense to form a cartilage anlage. Initially, all chondrocytes within the anlage proliferate. Thereafter, cells in the center of this structure exit the cell cycle, undergo hypertrophy, which is a hallmark of terminal differentiation, and eventually die. Concomitantly, a bone collar is formed from the perichondrium surrounding the cartilaginous core. After apoptosis of the hypertrophic chondrocytes, blood vessels invade the cartilage and form the bone marrow cavity; blood vessels are also thought to bring in osteoblasts that produce the endochondral bone. Upon formation of the bone marrow cavity, immature chondrocytes are restricted to the ends of the cartilage that form the growth region, where cells undergo an orderly progression from proliferation to
Synergistic induction of matrix metalloproteinase 1 by interleukin-1 alpha and oncostatin M in human chondrocytes involves signal transducer and activator of transcription and activator protein 1 transcription factors via a novel ...
Supplementary Materials1. all chondrocytes and osteoblasts3. Sox9 binds to genes encoding major cartilaginous matrix proteins such as aggrecan (and regulates their expression. How these early osteochondroprogenitors and their descendants relate to mesenchymal precursors in adult bone is unknown. In adult endochondral bones, the source of osteoblasts and stromal cells has been proposed to be mesenchymal stem cells (MSCs) or bone marrow stromal/mesenchymal progenitor cells (BMSCs), which are traditionally defined as cells capable of forming colonies (CFU-Fs: colony forming unit-fibroblasts) that can undergo multilineage differentiation and upon transplantation4. CFU-Fs are enriched among numerous adult marrow populations such as gene promoter/enhancers might encompass mesenchymal precursors of osteoblasts and stromal cells. Earlier studies BI-1356 biological activity show that osteochondroprogenitors are designated by recombinases driven with the promoter9C12. First, we mapped cell fates utilizing ...
Staines, K A and Poulet, B and Farquharson, C and Pitsillides, A A (2013) STABILISING CARTILAGE TO INNATELY PROTECT AGAINST OSTEOARTHRITIS: LESSONS FROM LONG BONE DEVELOPMENT. In: UNSPECIFIED. Full text not available from this repository ...
Differentiation into chondrocytes[edit]. Main article: Chondrocyte. Chondrocytes are only present in cartilage where they will ... During this process, TGF-β can stimulate differentiation into either chondrocytes or osteoblasts via FGF, Msx1, and Ctgf ... They have the ability to differentiate into osteoblasts or chondrocytes depending on the signalling molecules they are exposed ... Lefebvre, V; Behringer RR; de Crombrugghe B (2001). "L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte ...
The primary center In long bones, bone tissue first appears in the diaphysis (middle of shaft). Chondrocytes multiply and form ...
1996). "Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase". J. Biol. Chem. ...
Loeser RF (2002). "Integrins and cell signaling in chondrocytes". Biorheology. 39 (1-2): 119-24. PMID 12082274. Overview of all ...
Expression of ENaC, Na+/K+/2Cl- cotransporter and Na+/H+ exchangers in healthy and arthritic chondrocytes". Histol. Histopathol ... "Sodium transport systems in human chondrocytes. II. ...
The chondrocytes are grown and injected into the defect under a periosteal patch. ACI surgery has reported good to excellent ... In this surgery, chondrocytes are arthroscopically extracted from the intercondylar notch of the articular surface. ... One such technique is autologous chondrocyte implantation (ACI), which is useful for large, isolated femoral defects in younger ... Open growth plates are characterized by increased numbers of undifferentiated chondrocytes (stem cells) which are precursors to ...
The chondrocytes present different morphologies related to their position in the tissue. The embryos of Sepia officinalis ... It is a vesicular cell-rich cartilage due to the large, spherical and vacuolated chondrocytes with no homologies in other ... Nutrition is supplied to the chondrocytes by diffusion. The compression of the articular cartilage or flexion of the elastic ... The odontophore contains muscle cells along with the chondrocytes in the case of Lymnaea and other mollusks that graze ...
MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes. In biology, oligopotency is the ability of progenitor ...
Some examples of chondrocytes include collagen and proteoglycans. The chondrocytes that produce chondrocalcin are typically ... This calcium-binding protein comes from chondrocytes, which are cells that produce and maintain cartilage. ... "Chondrocalcin is internalized by chondrocytes and triggers cartilage destruction via an interleukin-1β-dependent pathway, ...
Functions include: Chondrocyte proliferation and bone growth; regulation of cell proliferation, cell adhesion and induction of ... It is expressed on chondrocytes and cardiac muscle. Involved in growth plate morphogenesis and function. Integrin α11β1 is ...
"Synthesis of classical pathway complement components by chondrocytes". Immunology. 88 (4): 648-56. PMC 1456645. PMID 8881771. ...
... a homeoprotein selectively expressed in chondrocytes". Proceedings of the National Academy of Sciences of the United States of ...
It is also found near chondrocytes (cartilage-forming cells). Chondrocytes play a vital role in osteogenesis (the formation of ... Though some chondrocytes do manage to survive, growth is significantly reduced, resulting in the characteristically short limbs ... It is observed at a high frequency in chondrocytes in developing bone and tendon. In pseudochondroplasia, COMP is not secreted ... The researchers found that IX collagen was amassed within the pseudoachondroplasia chondrocytes. This discovery suggests that ...
Remaining chondrocytes divide in order to form more chondroblasts. HMGB-1, a growth factor which promotes chondrocyte division ... Chondroblasts are called chondrocytes when they embed themselves in the cartilage matrix, consisting of proteoglycan and ... These cells are extremely important in chondrogenesis due to their role in forming both the chondrocytes and cartilage matrix ... Higher levels of Wnt14 prevented chondrocyte differentiation whereas lower levels appeared to allow it. If the Wnt/ β-Catenin ...
"ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes". Biochemical and Biophysical Research ... inhibition enhances aggrecan deposition and suppresses matrix metalloproteinase-3 production in human articular chondrocytes". ...
... also has an antiapoptotic effect in osteoarthritic chondrocytes. The precise role of ADAM15 in cancer is still unclear ... 1997). "Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes". ... "ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of the X-linked inhibitor of apoptosis ...
2000). "Regulation of human COL2A1 gene expression in chondrocytes. Identification of C-Krox-responsive elements and modulation ...
... where they are subsequently dissipated and transmitted to chondrocytes (cartilage cells). Chondrocytes sense and convert the ... there need to be mechanoreceptors on the surface of chondrocytes. Candidates for chondrocyte mechanoreceptors include stretch- ... Each chondrocyte has one cilium and it is hypothesized to transmit mechanical signals by way of bending in response to ECM ... Chondrocytes have been shown to secrete TGF-b, and upregulate TGF-b receptors in response to mechanical stimulation; this ...
... structure and transcription pattern in chondrocytes". The Biochemical Journal. 303. 303 ( Pt 1): 329-33. doi:10.1042/bj3030329 ...
They are usually highly expressed in cartilage and within chondrocytes. Their genetic transcription increases upon the ...
Craft AM, Ahmed N, Rockel JS, Baht GS, Alman BA, Kandel RA, Grigoriadis AE, Keller GM (2013). "Specification of chondrocytes ... chondrocytes, T lymphocytes and myeloid precursors. Keller holds a Tier I Canada Research Chair in Embryonic Stem Cell Biology ...
2002). "Human articular chondrocytes express three facilitative glucose transporter isoforms: GLUT1, GLUT3 and GLUT9". Cell ... The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript ... "Cytokine regulation of facilitated glucose transport in human articular chondrocytes". J. Immunol. 167 (12): 7001-8. doi: ... characterization and partial cDNA cloning of facilitative glucose transporters expressed in human articular chondrocytes; ...
Ihh stimulates chondrocyte proliferation and regulates chondrocyte maturation by maintaining the expression of PTHrP. PTHrP ... Because chondrocytes are bound in lacunae, they cannot migrate to damaged areas. Also, because hyaline cartilage does not have ... The expression of Sox9 induces the expression of BMP, which causes chondrocytes to proliferate and differentiate. L-Sox5 and ... The molecule Indian hedgehog (Ihh) is expressed by prehypertrophic chondrocytes. ...
Steroids that are released as a result kill the chondrocytes. The remaining chondrocytes have trouble exchanging nutrients with ... When pressure is exerted on the joint, fluids move between the chondrocytes and synovial fluid, exchanging nutrients. In ...
Chondrocytes are found in cartilage and produce the cartilaginous matrix. Osteoblasts are responsible for bone formation. The ... Allen JL, Cooke ME, Alliston T (September 2012). "ECM stiffness primes the TGFβ pathway to promote chondrocyte differentiation ...
Effectively, FGF-3 inhibits proliferation of chondrocytes within growth plate. FGF family members possess broad mitogenic and ...
1999-01-01). "Aggrecan degradation in chondrocytes is mediated by reactive oxygen species and protected by antioxidants". Free ... 2012-03-27). "l-Carnitine enhances extracellular matrix synthesis in human primary chondrocytes". Rheumatology International. ... Possible link with the reduction in chondrocyte apoptosis and caspase 3 level". Arthritis & Rheumatism. 43 (6): 1290-1299. doi: ...
the chondrocytes only make up 2% of the tissue's volume. chondrocytes and the extracellular matrix are contained in an ... Similarly to hyaline one or multiple chondrocytes lie between the spaces (or lacunea) in the fibres. ...
Studies in chondrocyte cell line has revealed nearly 50% of SOX9 is bound to DNA and it is directly regulated by external ... It is expressed by proliferating but not hypertrophic chondrocytes that is essential for differentiation of precursor cells ... Lefebvre V, de Crombrugghe B (March 1998). "Toward understanding SOX9 function in chondrocyte differentiation". Matrix Biology ... "Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte- ...
"Cartilage and Chondrocytes", in Gary Feinstein et al. Kelley and Firesteins Textbook of Rheumatology, 10th edition (2017) ... Chondrocytes (from Greek χόνδρος, chondros = cartilage + κύτος, kytos = cell) are the only cells found in healthy cartilage. ... The chondrocyte in cartilage matrix has rounded or polygonal structure. The exception occurs at tissue boundaries, for example ... Although the word chondroblast is commonly used to describe an immature chondrocyte, the term is imprecise, since the ...
Nasal chondrocytes (NC) are present in the hyaline cartilage of the nasal septum, and in fact are the only cell type within the ... Similar to chondrocytes present in articular cartilage, NC express extracellular matrix proteins such as glycosaminoglycans and ... Pelttari K, Mumme M, Barbero A, Martin I 5/25/2017 Nasal chondrocytes as a neural crest-derived cell source for regenerative ... Liese J, Marzahn U, El SK, Pruss A, Haisch A, Stoelzel K 6/2013 Cartilage tissue engineering of nasal septal chondrocyte- ...
The cytochrome b558 content in chondrocytes was about 10 pmol/mg of proteins: this amount is lower than in neutrophils (200 ... The O2- produced by chondrocyte NADPH oxidase is about 0.1% of the respiratory burst measured in phagocytic cells such as ... The low level of superoxide anions O2- produced by chondrocytes in comparison with neutrophils may be involved in signal ... This work shows that three different human immortalized chondrocyte (HIC) cell lines (a gift from M Goldring) and native ...
Canine Chondrocytes: CnC (Cryovial); find Sigma-Aldrich-CN402-05 MSDS, related peer-reviewed papers, technical documents, ... Canine Chondrocytes (CnC) were utilized to evaluate anti-inflammatory and anti-oxidant activity of Glyco-Flex III (Yáñez, 2008 ... Canine Chondrocytes (CnC) are derived from normal canine articular cartilage where they produce and maintain the extracellular ... Following monolayer culturing, CnC can be grown in alginate microspheres to study chondrocyte proliferation and metabolism in a ...
... and signaling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis, and regulate chondrocyte-specific ... Chondrocytes express several members of the integrin family, including α5β1, the primary chondrocyte receptor for fibronectin. ... These chondrocyte integrins have a potential role in the initial adhesion and retention of chondrocytes at a cartilage defect ... TNF and IL-1 or anti-Fas antibody growth-regulated oncogene α in ECM can induce chondrocyte apoptosis. Chondrocyte apoptosis ...
We observed a significant correlation between MMP13 mRNA levels and RUNX2 gene expression in human OA chondrocytes. RUNX2 ... A significant negative correlation was observed between RUNX2 mRNA levels in OA chondrocytes and the percentage methylation of ... We and others have shown that the abnormal MMP13 gene expression in OA chondrocytes is controlled by changes in the DNA ... of the methylation status of specific CpG sites in the RUNX2 promoter on RUNX2-driven MMP13 gene expression in OA chondrocytes ...
Chondrocytes Articular Cartilage The formation and maintenance of articular cartilage depends on chondrocytes.1,4,5 These are ... You are here: Home1 / Blog2 / Musculoskeletal Medicine3 / Biology4 / Articular Cartilage5 / Chondrocytes ...
BCP crystals promote chondrocyte hypertrophic differentiation in OA cartilage by sequestering Wnt3a Jessica Bertrand, Tabea ...
An innovative strategy for delivering drugs to chondrocytes in situ offers new avenues for treating osteoarthritis (Geiger et ... An innovative strategy for delivering drugs to chondrocytes in situ offers new avenues for treating osteoarthritis (Geiger et ...
Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. Our results obtained on two ... and also in primary culture of chondrocytes under H,sub,2,/sub,O,sub,2,/sub, injury. The experiments were done on healthy ... animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative ... Primary Chondrocytes. Primary chondrocytes were isolated from the normal articular cartilage of Wistar rats by collagenase II ( ...
Autologous cultured chondrocytes are the patients own cartilage cells. The cells are removed from the patient and sent to a ... Autologous cultured chondrocytes are used, as part of an overall program (that includes knee surgery and special exercises), to ...
Passage 2 chondrocytes were randomly divided into four groups and treated with EA or nocodazole. After treatment, cell ... The expression levels of cyclin D1, CDK4, CDK6 and Rb were higher in chondrocytes receiving EA treatment when compared to ... The aim of the present study was to investigate the effects of electroacupuncture (EA) on the proliferation of chondrocytes and ... Electroacupuncture promotes chondrocyte proliferation via accelerated G1/S transition in the cell cycle ...
... J Bone Joint Surg Br. 2009 Aug;91(8):997-1006. doi: 10.1302/0301-620X. ... Autologous chondrocyte implantation may be used for full-thickness chondral or osteochondral injuries which are painful and ... The formation of hyaline or hyaline-like cartilage may be induced by implanting autologous, cultured chondrocytes into the ... We provide a review of autologous chondrocyte implantation and describe our experience with the technique at our institution ...
FILGUEIRAS, R.R et al. Effect of freezing on rabbit cultured chondrocytes. Arq. Bras. Med. Vet. Zootec. [online]. 2011, vol.63 ... Fresh chondrocytes showed a high mitotic rate and abundant matrix was present up to 60 days of culture. Loss of phenotypic ... Chondrocytes extracted from joint cartilage of nine healthy New Zealand White rabbits were cultivated and frozen with the ... Furthermore, the chondrocytes should be implanted after two weeks of culture, when the highest viability rate is found ...
After 15 days of culture, the fresh chondrocytes of one flask and the thawed chondrocytes of another were fixed in 4% ... The chondrocytes were then post-fixed for four hours in 1% OsO4 diluted in PBS, pH 7.4, at 4ºC. Dehydration with ethanol and ... Chondrocyte death associated with human femoral osteochondral harvest as performed for mosaycplasty. J. Bone Jt. Surg., v.87-A ... The thawed chondrocytes showed a slow confluence rate with a mean of 50% three days after thawing. A 75% confluence rate was ...
Rat maf related genes: specific expression in chondrocytes, lens and spinal cord.. Sakai M1, Imaki J, Yoshida K, Ogata A, ... studies and in situ hybridization analyses show that maf-1 and maf-2 are strongly expressed in the late stages of chondrocyte ...
To determine whether differentiated chondrocytes are motile.. DESIGN: Calf articular chondrocytes isolated from six animals ... Motile chondrocytes from newborn calf: migration properties and synthesis of collagen II.. Chang C1, Lauffenburger DA, Morales ... In Boyden chambers, locomotion of day 3 chondrocytes on fibronectin-coated membranes was approximately 3-fold higher than on ... A population of well-differentiated chondrocytes capable of matrix (COL II) synthesis are motile in vitro. This original ...
Autologous Cultured Chondrocytes for Implantation) may treat, uses, dosage, side effects, drug interactions, warnings, patient ... Autologous cultured chondrocytes, the Carticel product, are derived from in vitro expansion of chondrocytes harvested from the ... Chondrocyte labeling in one of the rabbit studies8 and in an independent study in goats by DellAccio et al10 demonstrated that ... Bioactivity of autologous chondrocytes implanted under a periosteal patch was reported in the BLA for three rabbit studies6,7,8 ...
... counteracts effects of an inflammatory environment on genes regulating matrix degradation and formation in human chondrocytes. ... Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes Am J Sports Med. 2011 Nov;39(11): ... Methods: Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. ... Although anabolic effects of PRP on chondrocytes are well documented, no reports are known addressing effects on cartilage ...
Specification of chondrocytes and cartilage tissues from embryonic stem cells April M. Craft, Nazish Ahmed, Jason S. Rockel, ... Summary: Characterization of a zebrafish model of SMMD reveals that the transcription factor Nkx3.2 fine-tunes chondrocyte ... FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth ... biosynthesis in mesenchymal cells or chondrocytes shows that precise regulation of biosynthesis is required for chondrocyte ...
"Chondrocytes" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... This graph shows the total number of publications written about "Chondrocytes" by people in Harvard Catalyst Profiles by year, ... Calreticulin regulates a switch between osteoblast and chondrocyte lineages derived from murine embryonic stem cells. J Biol ... Evolutionary Selection and Constraint on Human Knee Chondrocyte Regulation Impacts Osteoarthritis Risk. Cell. 2020 04 16; 181(2 ...
The Mammalian Phenotype (MP) Ontology is a community effort to provide standard terms for annotating phenotypic data. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated phenotype data at MGI are provided in Term Detail reports.
Bovine articular chondrocytes were encapsulated in the hydrogels and cultured for 14 days. The influence of hydrogel stiffness ... However, the influence of each property on chondrocyte phenotype is unclear due to the difficulty in separating the roles of ... In this study, we aimed to study the influence of hydrogel stiffness on chondrocyte phenotype while excluding the role of ... Both the mechanical and biochemical properties of hydrogels can affect the phenotype of chondrocytes. ...
... the chondrocyte-selective Bmal1-KO mouse model allows proper evaluation of the roles of chondrocyte-expressed BMAL1 and ... The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. Michal Dudek,1 Nicole Gossan,1 Nan Yang,1 Hee- ... Deletion of chondrocyte Bmal1 leads to cartilage-specific loss of circadian rhythm. (A) Representative BMAL1 IHC (brown) in WT ... F) ALK1 and ALK5 levels were measured by qPCR in primary human articular chondrocytes following knockdown of BMAL1 (n = 3 ...
This invention provides a system for obtaining cells of the chondrocyte lineage by differentiating primate pluripotent stem ... or other products that are characteristic of the chondrocyte lineage. Chondrocytes and chondrocyte precursor cells obtained ... Chondrocytes in Clinical Therapy This invention also provides for the use of chondrocyte precursor cells and their derivatives ... Driving Differentiation towards Chondrocytes In order to direct the culture towards the chondrocyte pathway, pPS cells that ...
Together, these results define a regulatory mechanism that links chondrocyte BMAL1 to the maintenance and repair of cartilage ... Furthermore, targeted Bmal1 ablation in mouse chondrocytes abolished their circadian rhythm and caused progressive degeneration ...
Bovine primary chondrocytes isolated from the femoral condyles were used in all the experiments for neocartilage production. ... 2. Hypertonic conditions enhance cartilage formation in scaffold-free primary chondrocyte cultures. Open this publication in ... Primary chondrocyte, Tissue engineering, Oxygen tension, Glucosamine sulphate, Cell culture, Neocartilage National Category ... Production of neocartilage tissues using primary chondrocytes. Ylärinne, Janne Umeå University, Faculty of Medicine, Department ...
... Author(s). Ragan, Paula Marie ...
... chondrocyte explanation free. What is chondrocyte? Meaning of chondrocyte medical term. What does chondrocyte mean? ... Looking for online definition of chondrocyte in the Medical Dictionary? ... Related to chondrocyte: chondroblast, Eosinophils, Autologous Chondrocyte Implantation. chondrocyte. [kon´dro-sīt] one of the ... Chondrocyte , definition of chondrocyte by Medical dictionary https://medical-dictionary.thefreedictionary.com/chondrocyte ...
  • Although the word chondroblast is commonly used to describe an immature chondrocyte, the term is imprecise, since the progenitor of chondrocytes (which are mesenchymal stem cells ) can differentiate into various cell types, including osteoblasts . (wikipedia.org)
  • In this work, articular chondrocytes (ACs) and mesenchymal stem cells (MSCs) with 1:1 and 1:3 cell ratios were co-cultured in order to evaluate if a majority of primary ACs can be replaced with MSCs without detrimental effects on in vitro chondrogenesis. (rice.edu)
  • Following monolayer culturing, CnC can be grown in alginate microspheres to study chondrocyte proliferation and metabolism in a three-dimensional in vitro system. (sigmaaldrich.com)
  • A population of well-differentiated chondrocytes capable of matrix (COL II) synthesis are motile in vitro. (nih.gov)
  • Autologous cultured chondrocytes, the Carticel product, are derived from in vitro expansion of chondrocytes harvested from the patient's normal, femoral articular cartilage. (rxlist.com)
  • 4. A population of chondrocyte progenitors that proliferates in an in vitro culture, obtained by differentiating primate pluripotent stem (pPS) cells, and capable of forming progeny having the characteristics of the cells of claim 1. (freepatentsonline.com)
  • Jeong, C.G. and Hollister, S.J. (2010) A comparison of the influence of material on in vitro cartilage tissue engineering with PCL, PGS and POC 3D scaffold architecture seeded with chondrocytes. (scirp.org)
  • These results suggest that T-2 toxin and/or DON inhibit proliferation and induce apoptosis through a possible mechanism involving reactive oxygen species-mediated mitochondrial pathway that is not specific for chondrocytes in vitro or joint tissues in vivo . (nature.com)
  • For successful cartilage tissue engineering, the ability to generate a high number of chondrocytes in vitro while avoiding terminal differentiation or de-differentiation is critical. (rti.org)
  • In vitro re-differentiation capacity was assessed after a 6-week induction, and chondrocytes grown in Low-SFM showed similar expression ratios of COL2/COL1 and ACAN/VCAN to native cartilage. (rti.org)
  • In vivo and in vitro treatment with N -acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. (rupress.org)
  • We investigated the effect of glucosamine in an in vitro model of cartilage collagen degradation in which collagen degradation induced by activated chondrocytes is mediated by lipid peroxidation reaction. (chiro.org)
  • Together, the data suggest that the mechanism of decreasing collagen degradation in this in vitro model system by glucosamine may be mediated by the inhibition of advanced lipoxidation reaction, preventing the oxidation and loss of collagen matrix from labeled chondrocyte matrix. (chiro.org)
  • PKH 26劌 is a relatively new cell-labeling agent, but few data exist on the application of this dye in chondrocytes in vitro and in vivo. (scirp.org)
  • The third aim was to compare the duration of cell labeling of chondrocytes of different origin with established CMFDA as stan-dard and PKH 26潴 for 3 cell generations in vitro and 12 weeks in vivo. (scirp.org)
  • The PKH 26潴 labeled articular chondrocytes maintained fluorescence longer than CMFDA in vitro and in vivo. (scirp.org)
  • We test the feasibility of this hypothesis by examining the ability of chondrocytes to present antigen to CTL in vitro. (wellnessresources.com)
  • We found that upregulating Ihh signaling in the developing cartilage by treating PTHrP -/- limb explants with sonic hedgehog (Shh) protein in vitro, or overexpressing Ihh in the cartilage of PTHrP -/- embryos or inactivating patched 1 ( Ptch1 ), a negative regulator of hedgehog (Hh) signaling, accelerated chondrocyte hypertrophy in the PTHrP -/- embryos. (biologists.org)
  • Persistence of collagen type II synthesis and secretion in rapidly proliferating human articular chondrocytes in vitro. (uio.no)
  • Next, we examined the effect of neutrophil elastase (NE) on chondrocytes in vitro and in vivo . (frontiersin.org)
  • The results showed that NE suppressed cell proliferation, induced apoptosis and prevented cell migration in chondrocytes in vitro , accompanied by the elevation of intracellular ROS and calcium level. (frontiersin.org)
  • In vitro experiments with chondrocytes in culture have demonstrated a variety of physiological and biochemical responses to cyclical mechanical stimuli. (rupress.org)
  • Edible Bird's nest extract as a chondro-protective agent for human chondrocytes isolated from osteoarthritic knee: in vitro study. (biomedsearch.com)
  • CONCLUSION: Edible Bird's Nest extract coded as HMG demonstrated chondro-protection ability on human articular chondrocytes in vitro. (biomedsearch.com)
  • In vitro, dans les chondrocytes humains qui ont été traités avec différents médiateurs de l'inflammation, nous avons observé une augmentation de l'expression de la L-PGDS dose et temps dépendante. (umontreal.ca)
  • In vitro, human chondrocytes were treated with different inflammatory mediators (interleukin-1 beta, interleukin-17, hydrogen peroxide and tert-Butyl hydroperoxide). (umontreal.ca)
  • We discovered that chondrocytes release L-PGDS into the extracellular space in response to inflammation, in vivo and in vitro. (umontreal.ca)
  • To assess these findings in an in vitro model, primary cultures of immature articular chondrocytes were incubated with four quinolone solutions: ofloxacin, ciprofloxacin, nalidixic acid at 10 micrograms/ml for 24 hr and pefloxacin at 1, 10 and 100 micrograms/ml for various periods of time (2, 4, 6, 12, 24 and 48 hr). (aspetjournals.org)
  • Quinolones induce in vitro an early stimulation of the oxidative metabolism in immature but not in mature chondrocytes, a phenomenon that could explain juvenile onset of quinolone arthropathy. (aspetjournals.org)
  • Our study suggests that hesperidin can prevent H₂O₂-induced chondrocytes injury through its antioxidant effects in vitro and reduce cartilage damage in a rat model of OA. (medscimonit.com)
  • Conditional ablation of Fgfr1 and Fgfr2 in the osteoblast lineage in mouse reveals a feed-forward loop controlling FGFR3 signaling in growth plate chondrocytes. (biologists.org)
  • Our findings show that types II and X collagen interacted with cell surface-expressed annexin V. These interactions led to a stimulation of annexin V-mediated Ca 2+ influx resulting in an increased intracellular Ca 2+ concentration, [Ca 2+ ] i , and ultimately increased alkaline phosphatase activity and mineralization of growth plate chondrocytes. (pubmedcentralcanada.ca)
  • Just before mineralization starts, type II collagen synthesis is reduced and the hypertrophic growth plate chondrocytes produce type X collagen ( 2 , 3 ). (pubmedcentralcanada.ca)
  • Several cell surface receptors that mediate cell/matrix interactions have been identified in growth plate chondrocytes. (pubmedcentralcanada.ca)
  • Several integrins have been identified to be expressed by growth plate chondrocytes. (pubmedcentralcanada.ca)
  • We and others have shown that annexin V, among other annexins, is highly expressed by hypertrophic and terminally differentiated growth plate chondrocytes ( 9 , 10 ). (pubmedcentralcanada.ca)
  • We provided evidence that annexin V mediates Ca 2+ influx into growth plate chondrocytes and that this annexin-mediated Ca 2+ influx regulates terminal differentiation and mineralization events ( 16 , 17 ). (pubmedcentralcanada.ca)
  • The traditional view was that growth hormone acted indirectly on the growth plate via IGF-I, a potent mitogen for growth plate chondrocytes. (unu.edu)
  • In addition to having effects on the growth plate chondrocytes, locally synthesised and circulating IGFs retained in bone matrix are important in the regulation of bone remodelling. (unu.edu)
  • BSHXF significantly recovered the OVX-induced abnormal osteogenesis and adipogenesis with the activation of β-catenin in growth plate chondrocytes. (em-consulte.com)
  • BSHXF attenuates osteoporosis by promoting osteogenic differentiation of growth plate chondrocytes mainly in β-catenin-dependent manner. (em-consulte.com)
  • Chondrocytes undergo terminal differentiation when they become hypertrophic , which happens during endochondral ossification . (wikipedia.org)
  • From least- to terminally-differentiated, the chondrocytic lineage is: Colony-forming unit-fibroblast Mesenchymal stem cell / marrow stromal cell Chondrocyte Hypertrophic chondrocyte Mesenchymal (mesoderm origin) stem cells are undifferentiated, meaning they can differentiate into a variety of generative cells commonly known as osteochondrogenic (or osteogenic, chondrogenic, osteoprogenitor, etc.) cells. (wikipedia.org)
  • In addition to the delay, chondrocytes in the transgenic mice initially become hypertrophic at the periphery of the developing long bones rather than in the middle, leading to a seeming reversal in the pattern of chondrocyte differentiation and ossification. (pnas.org)
  • The chondrocyte dedifferentiation marker Col1a1 and hypertrophic marker Col10a1 were significantly downregulated with the inclusion of Klf4 (P (sigmaaldrich.com)
  • Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. (rupress.org)
  • Elevated ROS levels are detected in hypertrophic chondrocytes. (rupress.org)
  • These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes. (rupress.org)
  • Chondrocytes then stop dividing and increase their volume dramatically, becoming hypertrophic ( 2 ). (rupress.org)
  • Hypertrophic chondrocytes, which also produce matrix metalloproteinase (MMP) 13, die by apoptosis ( 1 - 3 ). (rupress.org)
  • Hypertrophic chondrocytes express vascular endothelial growth factor, stimulating blood vessels to invade the cartilage model ( 2 ). (rupress.org)
  • In addition, inhibition of the mTORC1 pathway via rapamycin treatment blocks mechanical induction of Indian hedgehog (Ihh), a central mediator of mechanical regulation of chondrocyte proliferation and differentiation, while selective inhibition of PKC-a, a downstream target of mTORC2 blocked mechanical stimulation of the expression of chondrocyte hypertrophic marker collagen X. Furthermore, deficiency of SH2-containing protein tyrosine phosphatase 2 (Shp2) enhances mechanical stimulation of mTORC1. (lifespan.org)
  • Eventually, the most mature hypertrophic chondrocytes undergo apoptosis. (biologists.org)
  • The hypertrophic chondrocytes secrete vascular endothelia growth factor (Vegf) and matrix metalloproteinases (Mmps), which will degrade the extracellular matrix and allow the invasion of blood vessels and osteoblasts differentiated in the perichondrium to form the trabecular bone. (biologists.org)
  • In the middle zone, chondrocytes are larger and more rounded and display a random distribution, in which the collagen fibers also are more randomly arranged. (wikipedia.org)
  • In the deeper zones, chondrocytes form columns that are oriented perpendicular to the cartilage surface, along with the collagen fibers. (wikipedia.org)
  • Similar to chondrocytes present in articular cartilage, NC express extracellular matrix proteins such as glycosaminoglycans and collagen. (wikipedia.org)
  • Loss of phenotypic stability was notable in the thawed chondrocytes, with a low labeling of proteoglycans and weak immunostaining of type II collagen. (scielo.br)
  • Motile chondrocytes from newborn calf: migration properties and synthesis of collagen II. (nih.gov)
  • Progeny are capable of synthesizing Type II collagen or aggrecan, or other products that are characteristic of the chondrocyte lineage. (freepatentsonline.com)
  • One goal of the study was to determine how crosslinking and pH variations affect the cell viability of chondrocytes and the mechanics, gelation kinetics and printability of collagen bioinks. (thefreedictionary.com)
  • Herein, we report that overexpression of PTHrP in chondrocytes using the mouse type II collagen promoter induces a novel form of chondrodysplasia characterized by short-limbed dwarfism and a delay in endochondral ossification. (pnas.org)
  • Chondrocytes transduced with Ad-BMP-2 demonstrated greater cell numbers and significantly greater expression of chondrogenic markers including aggrecan, collagen II, and proteoglycan through 14 days of culture as compared to untransduced or Ad-GFP controls. (scirp.org)
  • Chondrocytes are also responsible for the biosynthesis of three crucial factors for joint health: Type II collagen, hyaluronic acid (HA, which acts as a cushion and lubricant in your joints), and chondroitin sulfate, which I'll explain below. (losethebackpain.com)
  • Only hydrolyzed type II collagen stimulates collagen biosynthesis, which stimulates the cartilage-making chondrocytes as undenatured collagen fails to do so according to at least one study [i] (collagen in its native or unhydrolyzed form has a large molecular structure too difficult for your body to use and absorb). (losethebackpain.com)
  • Lastly, the nanomechanical properties of cartilage cells (chondrocytes) and their aggrecan-collagen-rich pericellular matrix (PCM) were probed via AFM nanoindentation using both a sharp nano tip and a larger micro-colloidal tip to better understand the deformation of cells in cartilage. (mit.edu)
  • It is composed of only one specialized cell type, the chondrocytes, which produce and maintain the extracellular matrix of cartilage, i.e. collagen (mostly type II) and proteoglycans (primarily aggrecan). (promocell.com)
  • As chondrocytes divide, they form a columnar structure and secrete cartilage-specific extracellular matrix proteins, such as type II collagen and aggrecan ( 1 ). (rupress.org)
  • These large chondrocytes alter the matrix by secreting type X collagen and increased levels of fibronectin to promote mineralization by calcium carbonate. (rupress.org)
  • Glucosamine sulfate and glucosamine hydrochloride in millimolar (0.1 to 50) concentrations specifically and significantly inhibited collagen degradation induced by calcium ionophore-activated chondrocytes. (chiro.org)
  • Annexin V was identified as another protein binding to types II and X collagen, and it has been demonstrated that chondrocytes attach to type II collagen using annexin V ( 6 ). (pubmedcentralcanada.ca)
  • It was originally isolated from the chondrocyte membrane fractions as a type II collagen-binding protein ( 7 , 8 ). (pubmedcentralcanada.ca)
  • Cartilage is composed of a proteoglycan and collagen-rich extracellular matrix containing chondrocytes. (rupress.org)
  • Cell Multiplication and Type II Collagen Production by Rabbit Articular Chondrocytes Cultivated in a Defined Medium," Experimental CEll Research 155: 527-536 (1984). (patents.com)
  • Previously we have shown that the expression of RA-A47 (rheumatoid arthritis-related antigen) which is identical to HSP47, a collagen-binding chaperon, is downregulated in chondrocytes by tumor necrosis factor alpha (TNFalpha). (prohealth.com)
  • Chondrocytes (from Greek χόνδρος, chondros = cartilage + κύτος, kytos = cell) are the only cells found in healthy cartilage . (wikipedia.org)
  • The primary cilia are significant for spatial orientation of cells in developing growth plate and are sensory organelles in chondrocytes. (wikipedia.org)
  • This is mainly mediated by inflammation cells and resident cells such as chondrocytes. (springer.com)
  • The O 2- produced by chondrocyte NADPH oxidase is about 0.1% of the respiratory burst measured in phagocytic cells such as neutrophils. (springer.com)
  • The number of chondrocyte cells created and their maturation process can be influenced by multiple different genes and proteins. (wikipedia.org)
  • For chondrogenic cells, the treatment showed increased expression of the transcription factor Sox9, which plays a key role in chondrogenesis, the process of cartilage formation from condensed mesenchyme tissues, which then differentiate into chondrocytes. (wikipedia.org)
  • This process begins with a cartilage anlage where chondrocyte cells will congregate and start their maturation process. (wikipedia.org)
  • The formation and maintenance of articular cartilage depends on chondrocytes.1,4,5 These are derived from mesenchymal cells, which differentiate during skeletal morphogenesis. (orthogate.org)
  • Autologous cultured chondrocytes are the patient's own cartilage cells. (mayoclinic.org)
  • EA treatment significantly increased cell viability in a time-dependent manner and decreased the number of G0/G1 and G2/M phase chondrocytes and increased the number of S phase cells. (ingentaconnect.com)
  • The expression levels of cyclin D1, CDK4, CDK6 and Rb were higher in chondrocytes receiving EA treatment when compared to levels in the untreated cells while expression of P16 was lower. (ingentaconnect.com)
  • Each single use container of autologous cultured chondrocytes has approximately 12 million cells aseptically processed and suspended in 0.4 mL of sterile, buffered Dulbecco's Modified Eagles Medium (DMEM). (rxlist.com)
  • Conditional deletion of genes that regulate intracellular cholesterol biosynthesis in mesenchymal cells or chondrocytes shows that precise regulation of biosynthesis is required for chondrocyte homeostasis and long bone growth. (biologists.org)
  • Calreticulin regulates a switch between osteoblast and chondrocyte lineages derived from murine embryonic stem cells. (harvard.edu)
  • This invention provides a system for obtaining cells of the chondrocyte lineage by differentiating primate pluripotent stem cells. (freepatentsonline.com)
  • Chondrocytes and chondrocyte precursor cells obtained according to this disclosure are suitable for use in both research and clinical therapy. (freepatentsonline.com)
  • 8. A method for obtaining the cell population of claim 1, comprising differentiating the pPS cells, then culturing the differentiated cells with a mixture of chondrocyte differentiation factors. (freepatentsonline.com)
  • Our results describe the differences between the mitochondrial protein profiles of normal and OA chondrocytes, demonstrating that mitochondrial dysregulation occurs in cartilage cells during OA and highlighting redox imbalance as a key factor in OA pathogenesis. (mcponline.org)
  • There's a good chance, however, that you haven't heard about chondrocytes, which are the cells that form the cartilage in your body. (losethebackpain.com)
  • In people with severe knee pain, autologous chondrocyte implantation (ACI) is a recognized medical treatment that involves culturing chondrocyte cells (sourced from cartilage elsewhere in your body) and then implanting them into the damaged area. (losethebackpain.com)
  • Chondrocytes are essential for healthy joint function as they are the only cells that produce cartilage tissue. (losethebackpain.com)
  • We have developed for hESc a new 3-Stage directed differentiation protocol (DDP) to generate chondrocytes, the specialized cells that form cartilage tissue. (stembook.org)
  • We aimed to compare the cytotoxicity of T-2 toxin and DON on cell lines representative of cell types encountered in vivo , including human chondrocytes (C28/I2), human hepatic epithelial cells (L-02) and human tubular epithelial cells (HK-2). (nature.com)
  • Initially, mesenchymal cells are committed to become cartilage cells and condense into compact nodules and differentiate into chondrocytes. (rupress.org)
  • Chondrocyte hypertrophy is part of a normal differentiation process in which cells undergo apoptosis ( 1 , 2 ). (rupress.org)
  • The objective of our study is to compare the safety and effectiveness of the use of autologous cultured adipose tissue-derived stem cells versus cultured autologous chondrocytes for the treatment of chondral knee lesions. (clinicaltrials.gov)
  • It is worth mentioned that culture conditions are less stringent for ASC than for chondrocytes, in terms of number of passages to obtain the amount of cells needed for implantation. (clinicaltrials.gov)
  • We hypothesized that this association is due to in vivo articular cartilage chondrocyte senescence which causes an age‐related decline in the ability of th e cells to maintain articular cartilage, that is, increasing age increases the risk of OA because chondrocytes lose their ability to replace their extracellular matrix. (iospress.com)
  • New efforts to prevent the development or progression of OA might include strategies that delay the onset of chondrocyte senescence or replace senescent cells. (iospress.com)
  • Cartilage is produced by chondrocytes, specialised cells which make up only a small amount of the tissue. (thephysiotherapysite.co.uk)
  • CTL recognition of these cells is a potential mechanism for inflammation and cartilage damage, both through direct lysis of chondrocytes and the secretion of pro-inflammatory cytokines such as tumour necrosis factor and interferon-gamma (IFN-gamma). (wellnessresources.com)
  • However, treatment of chondrocytes with IFN-gamma up-regulated MHC class I expression and rendered the cells susceptible to lysis by CTL. (wellnessresources.com)
  • The latter is done using marrow stimulation techniques (such as microfracture), mosaicplasty (also known as osteochondral cylinder transplantation), and more recently with implantation of healthy cartilage cells (chondrocytes). (cochrane.org)
  • An alternative is autologous chondrocyte implantation (ACI), the surgical implantation of healthy cartilage cells into the damaged areas. (cochrane.org)
  • A morphological analysis of OA chondral tissue using light microscopy shows that the surface of the tissue is characterized by the presence of aggregated chondrocytes or "clones" but in the deeper areas isolated cells are found. (scielo.org.ar)
  • Finally, infected substrate-attached chondrocytes shifted to the nonpermissive temperature for transformation use fibronectin RNA more efficiently in protein synthesis than cells grown under the other conditions, suggesting for the first time a role for translational control of fibronectin gene expression. (rupress.org)
  • These condensed mesenchymal cells then differentiate into chondrocytes to form the cartilage anlagen. (biologists.org)
  • Many of the cell types present in the microenvironment of growing bone contribute to the local synthesis of cytokines and growth factors including the resident endothelial cells, marrow stromal cells, osteoblasts, periosteal cells and chondrocytes. (unu.edu)
  • Shahdadfar in this thesis presents an improved cell culture method for chondrocytes, which ensures that the cells maintain the ability to produce the right extracellular matrix. (uio.no)
  • Cyclical and static mechanical stimulation are well recognized as having a variety of effects on a number of different cell types, including bone cells, chondrocytes, vascular endothelium, and smooth muscle, from tissues normally exposed to mechanical forces. (rupress.org)
  • In immature chondrocyte cultures treated with pefloxacin, ofloxacin and nalidixic acid at 10 micrograms/ml for 24 hr, levels of cellular fluorescent dichlorofluorescein DCF (oxidized form of DCFH-DA) were significantly higher than in control cells. (aspetjournals.org)
  • To understand the significance of RA-A47 downregulation in chondrocytes independent from other effects of TNFalpha, we used an antisense oligonucleotide approach and investigated the effect of this treatment on the expression of molecules related to matrix degradation and production of growth factors for chondrocytic, endothelial, and synovial cells. (prohealth.com)
  • Furthermore, the stimulation of bFGF and CTGF release from chondrocytes may stimulate the proliferation of adjacent endothelial and/or synovial cells. (prohealth.com)
  • We found that smooth muscle cells (SMCs) gave rise to osteochondrogenic precursor- and chondrocyte-like cells in calcified blood vessels of matrix Gla protein deficient (MGP −/− ) mice. (ahajournals.org)
  • Although previously considered a degenerative, uncontrolled process, the presence of bone-related proteins, cells of osteoblast and chondrocyte morphology, and outright bone- and cartilage-like tissue in calcified lesions has underscored the active, cell-mediated nature of vascular calcification. (ahajournals.org)
  • In conclusion, our study confirms that pulsed ultrasound stimulation can induce proteoglycan synthesis in chondrocytes. (diva-portal.org)
  • In ataxia telangiectasia mutated ( Atm )-deficient ( Atm −/− ) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. (rupress.org)
  • Stimulation of adult chondrocyte metabolism by a thyroid-derived factor" J. Orthoped. (patentgenius.com)
  • Therefore, we hypothesize that activation of the mTOR signaling pathway through both mTORC1 and mTORC2 is required for mechanical stimulation of chondrocyte proliferation and differentiation and that mechanical activation of the mTOR signaling is negatively regulated by Shp2 in the mechanosomes in chondrocytes. (lifespan.org)
  • Chondrocyte function is regulated partly by mechanical stimulation. (rupress.org)
  • Chondrocytes from IL-4 knockout mice fail to show a membrane hyperpolarization response to cyclical mechanical stimulation. (rupress.org)
  • Using flow cytometry, we previously established in an ex vivo model that fluoroquinolones induce a stimulation of the oxidative metabolism in immature chondrocytes. (aspetjournals.org)
  • Lentiviral vector expression of Klf4 enhances chondrogenesis and reduces hypertrophy in equine chondrocytes. (sigmaaldrich.com)
  • Chondrocyte hypertrophy induces angiogenesis and mineralization. (rupress.org)
  • We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. (rupress.org)
  • Because inappropriate chondrocyte hypertrophy causes skeletal growth abnormalities such as dwarfism, control of hypertrophy is critical for normal longitudinal bone growth ( 4 - 6 ). (rupress.org)
  • However, signals triggering chondrocyte hypertrophy have not been identified. (rupress.org)
  • however, recently it has been shown to play a key role in chondrocyte hypertrophy co-ordinately with SOX9. (bl.uk)
  • Specific Aim 2: Determine whether mechanical activation of the mTORC2 cascade affects chondrocyte hypertrophy by regulating cytoskeleton assembly through PKC-a. (lifespan.org)
  • Chondrocyte hypertrophy is an essential process required for endochondral bone formation. (biologists.org)
  • Proper regulation of chondrocyte hypertrophy is also required in postnatal cartilage homeostasis. (biologists.org)
  • Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulating the onset of chondrocyte hypertrophy by forming a negative feedback loop, in which Ihh signaling regulates chondrocyte hypertrophy by controlling PTHrP expression. (biologists.org)
  • To understand whether there is a PTHrP -independent role of Ihh signaling in regulating chondrocyte hypertrophy, we have both activated and inactivated Ihh signaling in the absence of PTHrP during endochondral skeletal development. (biologists.org)
  • Conversely, when Hh signaling was blocked by cyclopamine or by removing Smoothened ( Smo ), a positive regulator of Hh signaling, chondrocyte hypertrophy was delayed in the PTHrP -/- embryo. (biologists.org)
  • Furthermore, we show that upregulated Hh signaling in the postnatal cartilage led to accelerated chondrocyte hypertrophy during secondary ossification, which in turn caused reduction of joint cartilage. (biologists.org)
  • Our results revealed a novel role of Ihh signaling in promoting chondrocyte hypertrophy independently of PTHrP , which is particularly important in postnatal cartilage development and homeostasis. (biologists.org)
  • In addition, we found that bone morphogenetic protein (Bmp) and Wnt/β-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy. (biologists.org)
  • Slowly proliferating periarticular chondrocytes differentiate into highly proliferative columnar chondrocytes, and then proliferative chondrocytes exit cell cycle and undergo hypertrophy. (biologists.org)
  • Furthermore, the proper regulation of chondrocyte hypertrophy is also necessary for maintaining the cartilage lining synovial joint surfaces, as abnormal chondrocyte hypertrophy in articular cartilage is associated with a common cartilage degenerative disease: osteoarthritis ( Poole, 1999 ). (biologists.org)
  • Ihh is one of the key signaling molecules controlling both chondrocyte hypertrophy and bone formation in the developing skeletal system. (biologists.org)
  • However, it remains to be elucidated whether Ihh signaling regulates chondrocyte hypertrophy exclusively through PTHrP , as Ihh signals directly to proliferating and prehypertrophic chondrocytes. (biologists.org)
  • Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). (uni-muenchen.de)
  • Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. (uni-muenchen.de)
  • Both the mechanical and biochemical properties of hydrogels can affect the phenotype of chondrocytes. (mdpi.com)
  • However, the influence of each property on chondrocyte phenotype is unclear due to the difficulty in separating the roles of these properties. (mdpi.com)
  • In this study, we aimed to study the influence of hydrogel stiffness on chondrocyte phenotype while excluding the role of biochemical factors, such as adhesion site density in the hydrogels. (mdpi.com)
  • In this research we therefore investigated a possible new and unknown function of MEF2C transcription factor as a potential genetic regulator of the permanent articular chondrocyte phenotype. (bl.uk)
  • Thus, based on our studies a new and critical function for transcription factor MEF2C in HACs has been identified, where it helps promote expression of the differentiated chondrocyte phenotype through mutual regulation with SOX9. (bl.uk)
  • These findings give important new insights into our understanding of the transcription factor networks that regulate expression of the articular chondrocyte phenotype. (bl.uk)
  • In this study, a biphasic gelatin solution/hydrogel system was established for the three-dimensional culture of bovine articular chondrocytes (BACs) to investigate the influence of gelatin solution viscosity on chondrocyte proliferation, ECM secretion and the maintenance of the chondrocyte phenotype. (rsc.org)
  • The results suggested that high-viscosity was more beneficial for the maintenance of the chondrocyte phenotype, while low viscosity was more beneficial for cell expansion. (rsc.org)
  • Articular cartilage ECM plays a crucial role in regulating chondrocyte metabolism and functions, such as organized cytoskeleton through integrin-mediated signaling via cell-matrix interaction. (hindawi.com)
  • article{15c6cf90-cda6-4c22-9774-d7f077e0b1ae, abstract = {We evaluated the durability of autologous chondrocyte transplantation grafts in 61 patients treated for isolated cartilage defects on the femoral condyle or the patella and followed up for a mean of 7.4 years (range, 5 to 11). (lu.se)
  • Canine Chondrocytes (CnC) were utilized to evaluate anti-inflammatory and anti-oxidant activity of Glyco-Flex III (Yáñez, 2008) and trans-pterostilbene (Remsberg, 2008). (sigmaaldrich.com)
  • Our results obtained on two animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative stress. (hindawi.com)
  • Since OA is characterized by a catabolic and inflammatory joint environment, the authors investigated whether PRP was able to counteract the effects of such an environment on human osteoarthritic chondrocytes. (nih.gov)
  • Platelet-rich plasma inhibits inflammatory effects of interleukin-1 (IL-1) beta on human osteoarthritic chondrocytes. (nih.gov)
  • Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta-mediated effects on human osteoarthritic chondrocytes, including inhibition of NFκB activation. (nih.gov)
  • Platelet-rich plasma releasate counteracts effects of an inflammatory environment on genes regulating matrix degradation and formation in human chondrocytes. (nih.gov)
  • Chondrocytes secrete pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), that may contribute to the progression of OA ( 11 ). (spandidos-publications.com)
  • Cytotoxic T lymphocytes recognize and lyse chondrocytes under inflammatory, but not non-inflammatory conditions. (wellnessresources.com)
  • Chondrocyte exposure to inflammatory stimuli in several arthritic conditions, including osteoarthritis, results in the well-characterized induction of extracellular matrix degrading proteinases, notably members of a disintegrin and metalloproteinase (ADAM) with thrombospondin domains and matrix metalloproteinase families. (dovepress.com)
  • Following damage, cartilage is exposed to neurovascular peptides, and in this study we hypothesized that substance P and bradykinin, alongside inflammatory cytokines, may modulate chondrocyte steady-state messenger RNA levels for the proteolytic ADAM family members as well as for key cytokines and neuropeptides. (dovepress.com)
  • We compared chondrocytes cultured in both two-dimensional and three-dimensional (3D) environments and found that 3D culture generally resulted in repression of expression of the genes under investigation, with the exception of anti-inflammatory interleukin 10 which was markedly upregulated in a 3D environment. (dovepress.com)
  • Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. (unboundmedicine.com)
  • Upon the initiation of the inflammatory process in osteoarthritis, chondrocytes try to save themselves by activating salvage pathways, among these pathways is the induction of L-PGDS gene. (umontreal.ca)
  • In this study we are addressing the signaling pathways involved in the regulation of (L-PGDS) gene expression, in chondrocytes treated with different inflammatory mediator. (umontreal.ca)
  • Whether TNF-beta induction of inflammatory pathways in primary human chondrocytes (PCH) can be modulated by resveratrol, was investigated. (uni-muenchen.de)
  • Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. (portlandpress.com)
  • Canine Chondrocytes (CnC) are derived from normal canine articular cartilage where they produce and maintain the extracellular matrix of cartilage. (sigmaaldrich.com)
  • 2009) Evaluation of extracellular matrix formation in polycaprolactone and starch-compounded polycaprolactone nanofiber meshes when seeded with bovine articular chondrocytes. (scirp.org)
  • Monolayer expansion of chondrocytes in culture results in the dedifferentiation of chondrocytes with inferior cartilage specific extracellular matrix synthesis and proliferation when compared with its native counterpart. (sigmaaldrich.com)
  • Chicken vertebral chondrocytes, which normally grow in suspension, synthesize large amounts of cartilage extracellular matrix proteins, but little fibronectin. (rupress.org)
  • Extracellular matrix (ECM), a highly dynamic structure, that synthesized by chondrocytes provides strength and tension in articular cartilage ( Goldring 2012 ). (frontiersin.org)
  • 2] may not induce chondrocyte apoptosis through caspase activation. (thefreedictionary.com)
  • Normal human chondrocytes were stimulated with interleukin (IL)-1β for 6 h to induce MMP expression, simulating a catabolic state, and then treated with pravastatin (1, 5 and 10 μM) for a further 18 h before cell lysates and supernatants were harvested. (springer.com)
  • Pefloxacin (10 micrograms/ml, 24 hr) did not induce any significant increase of DCFH-DA processing either in mature chondrocytes or in alveolar macrophages removed from immature rabbits. (aspetjournals.org)
  • The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA), and also in primary culture of chondrocytes under H 2 O 2 injury. (hindawi.com)
  • Yin MH, Wang YT, Li Q and Lv GF: Oligomeric proanthocyanidins inhibit apoptosis of chondrocytes induced by interleukin-1β. (spandidos-publications.com)
  • PTHrP may function in this regard to maintain the stepwise differentiation of chondrocytes that initiates endochondral ossification in the midsection of endochondral bones early in development and that also permits linear growth at the growth plate later in development. (pnas.org)
  • Another object of the present invention is to claim a method of enhancing the differentiation of chondrocytes and enhancing the synthesis of a cartilage specific matrix using tumor growth factor beta (TGF-.beta. (patents.com)
  • A Serum-Free Medium Supplemented With Multiplication-Stimulating Activity (MSA) Supports Both Proliferation and Differentiation of Chondrocytes in Primary Culture," Experimental Cell Research, 125: 167-174 (1980). (patents.com)
  • Proliferation and Differentiation of Chondrocytes in Defined Culture Medium Effects of Systematic Factors," Bone, 17: 558/117 (1995). (patents.com)
  • Mitochondrial proteins are attractive targets for the study of metabolism of the chondrocyte, the unique cell type present in mature cartilage, and its role in tissue degradation. (mcponline.org)
  • Zhang, H.-Q. Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls. (mdpi.com)
  • Wang Y-J, Yu H-G, Zhou Z-H, Guo Q, Wang L-J, Zhang H-Q. Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls. (mdpi.com)
  • In particular, cartilage tissues have abundant ECM that is viscoelastic and provides the necessary signals for the maintenance of chondrocyte activity and metabolism. (rsc.org)
  • The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. (umontreal.ca)
  • In human osteoarthritis chondrocytes, ET-1 controls the production of MMP-1 and MMP-13. (umontreal.ca)
  • Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. (portlandpress.com)
  • Cell culture studies of excess Vitamin A inhibits the synthesis of chondroitin sulfate by chondrocytes and causes the inhibition of chondrogenesis in the developing embryo which may result in limb malformations. (wikipedia.org)
  • 14. A method of screening a compound for its ability to modulate chondrocyte growth, differentiation, or synthesis of cartilage components, comprising combining the compound with the cell population of claim 1, determining any phenotypic or metabolic changes in the cell population that result from being combined with the compound, and correlating the change with an ability of the compound to modulate chondrocyte growth, differentiation, or synthesis of cartilage components. (freepatentsonline.com)
  • Ultrasound stimulates proteoglycan synthesis in bovine primary chondrocytes. (diva-portal.org)
  • We tested the efficacy of ultrasound to increase proteoglycan synthesis in bovine primary chondrocytes. (diva-portal.org)
  • For example, mitochondrial respiratory chain (MRC) activity in OA chondrocytes showed decreases in complexes I, II, and III compared with normal chondrocytes that caused a reduction in mitochondrial membrane potential (Δψm) and in ATP synthesis. (mcponline.org)
  • Furthermore, transformed chondrocytes have lost the ability to decrease fibronectin synthesis in response to suspension culture, suggesting that transformation alters the normal attachment-responsive control of fibronectin gene expression. (rupress.org)
  • Autologous cultured chondrocytes are used, as part of an overall program (that includes knee surgery and special exercises), to help repair damaged knee cartilage caused by acute or repetitive trauma in patients who had not responded to a prior arthroscopic or other surgical repair procedure. (mayoclinic.org)
  • Evolutionary Selection and Constraint on Human Knee Chondrocyte Regulation Impacts Osteoarthritis Risk. (harvard.edu)
  • Primary Human Chondrocytes isolated from normal human articular cartilage from the knee and hip joints. (promocell.com)
  • Primary Human Chondrocytes (HCH) are isolated from normal human articular cartilage from the knee and hip joints (lot specific source information is available on request). (promocell.com)
  • Knee articular chondrocytes obtained from 6‑week‑old SPF Kunming mice were cultured and serially passaged. (spandidos-publications.com)
  • During human evolution, the knee adapted to the biomechanical demands of bipedalism by altering chondrocyte developmental programs. (broadinstitute.org)
  • Today, osteoarthritis occurs in 250 million people, with risk variants enriched in non-coding sequences near chondrocyte genes, loci that likely became optimized during knee evolution. (broadinstitute.org)
  • We explore this relationship by epigenetically profiling joint chondrocytes, revealing ancient selection and recent constraint and drift on knee regulatory elements, which also overlap osteoarthritis variants that contribute to disease heritability by tending to modify constrained functional sequence. (broadinstitute.org)
  • Evidence-based recommendations on autologous chondrocyte implantation using chondrosphere (Spherox) for treating symptomatic articular cartilage defects of the knee in adults. (nice.org.uk)
  • Matrix-induced autologous chondrocyte implantation (MACI) is an established technique to treat articular cartilage defects in the knee. (springer.com)
  • Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. (springer.com)
  • Knee joint preservation with combined neutralising high tibial osteotomy (HTO) and matrix-induced autologous chondrocyte implantation (MACI) in younger patients with medial knee osteoarthritis: a case series with prospective clinical and MRI follow-up over 5 years. (springer.com)
  • Clinical and magnetic resonance imaging-based outcomes to 5 years after matrix-induced autologous chondrocyte implantation to address articular cartilage defects in the knee. (springer.com)
  • Basad E, Ishaque B, Bachmann G, Stürz H, Steinmeyer J. Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study. (springer.com)
  • Erggelet C, Sittinger M, Lahm A. The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. (springer.com)
  • Ronga M, Grassi FA, Bulgheroni P. Arthroscopic autologous chondrocyte implantation for the treatment of a chondral defect in the tibial plateau of the knee. (springer.com)
  • In the technique of autologous chondrocyte implantation (ACI), a small piece of cartilage is retrieved from the knee joint. (cochrane.org)
  • After publication of the first results of chondrocyte transplantation in patients with localized cartilage lesions of the knee joints by Brittberg et al. (ovid.com)
  • Chondrocytes obtained from biopsies of articular cartilage has for some time been used for treatment of focal lesions of the hyaline cartilage of the knee. (uio.no)
  • The present study aimed to investigate the effect of EBN extract on the catabolic and anabolic activities of the human articular chondrocytes (HACs) isolated from the knee joint of patients with OA. (biomedsearch.com)
  • Chondrocytes were isolated from rat knee joints and treated with hesperidin alone or combined with H₂O₂. (medscimonit.com)
  • Two proteins, bone morphogenetic protein 4(BMP-4) and fibroblast growth factor 2(FGF2) have been seen to influence the amount of differentiation into chondrocytes. (wikipedia.org)
  • Once the chondrocytes have fully matured at the desired rate, the cartilage tissue will harden into bone. (wikipedia.org)
  • The Runt-related transcription factor 2 (RUNX2) is critical for bone formation as well as chondrocyte maturation. (nature.com)
  • 10. The method of claim 8, wherein the mixture of chondrocyte differentiation factors comprises one or more factors selected from transforming growth factors (TGF), fibroblast growth factors (FGF), growth and differentiation factors (GDF), bone morphogenic proteins (BMP), hedgehog proteins (HH), L-ascorbic acid, and parathyroid hormone-related protein (PTHrP). (freepatentsonline.com)
  • This features a delay in chondrocyte differentiation and in bone collar formation and is sufficiently marked that the mice are born with a cartilaginous endochondral skeleton. (pnas.org)
  • This study evaluated chondrogenesis within a nanofiber polymeric scaffold seeded with isolated untreated chondrocytes, isolated chondrocytes genetically engineered with adenoviral (Ad) bone morphogenetic protein (BMP)-2, or isolated chondrocytes genetically engineered with green fluorescent protein (Ad-GFP). (scirp.org)
  • Chondrocytes then proliferate rapidly to form a model for the bone. (rupress.org)
  • In the developing long bones, chondrocytes undergo sequential proliferation and differentiation, which is required for proper longitudinal bone growth. (biologists.org)
  • During endochondral bone development, FGF9 and FGF18, derived from the perichondrium and surrounding tissue, signal to FGFR3 in chondrocytes. (wikipathways.org)
  • Further, we generated growth plate chondrocyte-specific β-catenin knockout ( β-catenin Gli1ER ) mice that exhibited bone loss and fat accumulation in the chondro-osseous junction, similar to the OVX mice. (em-consulte.com)
  • In vivo motility of chondrocytes remains an unexplored area [9]. (thefreedictionary.com)
  • These findings help explain the previously reported age related declines in chondrocyte synthetic activity and responsiveness to anabolic growth factors and indicate that in vivo articular cartilage chondrocyte senescence is responsible, at least in part, for the age related increased incidence of OA. (iospress.com)
  • Thus, we suggest that under certain circumstances CTL-mediated lysis of chondrocytes is potentially a potent mechanism for cartilage damage in vivo, but that low levels of MHC class I on healthy chondrocytes protects from immune recognition in health. (wellnessresources.com)
  • Méthode et conclusions: In vivo, l'arthrose a été suivie en fonction de l'âge chez la souris ou chirurgicalement suivant une intervention au niveau des genoux de souris. (umontreal.ca)
  • We and others have shown that the abnormal MMP13 gene expression in OA chondrocytes is controlled by changes in the DNA methylation status of specific CpG sites of the proximal promoter, as well as by the actions of different transactivators, including RUNX2. (nature.com)
  • The present study aimed to determine the influence of the methylation status of specific CpG sites in the RUNX2 promoter on RUNX2-driven MMP13 gene expression in OA chondrocytes. (nature.com)
  • We observed a significant correlation between MMP13 mRNA levels and RUNX2 gene expression in human OA chondrocytes. (nature.com)
  • We aimed to enhance chondrocyte proliferation and articular cartilage specific gene expression through ectopic expression of the major pluripotency transcription factors (Oct4, Sox2, Klf4 and c-Myc). (sigmaaldrich.com)
  • Modulation of fibronectin gene expression in chondrocytes by viral transformation and substrate attachment. (rupress.org)
  • The inhibition of miR-20a attenuated the calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhanced calcification in CEP chondrocytes on stiff matrix. (unboundmedicine.com)
  • The conditioned medium from LCS-treated macrophages promoted the proliferation, migration and maturation of chondrocytes. (rsc.org)
  • In a chondrocyte and macrophage co-culture system, LCS scaffolds induced chondrocyte maturation. (rsc.org)
  • These results demonstrated that LCS significantly promoted chondrocyte maturation by immunomodulating the M2 macrophage polarization. (rsc.org)
  • These results indicate that H 2 O 2 induces a rapid apoptosis via a mitochondrial pathway in rabbit chondrocytes. (spie.org)
  • The results of our study suggested that NE is an important factor in OA, which induces chondrocyte apoptosis and facilitates the occurrence of OA via caspase signaling pathway, and targeting the crucial signal centering around NE may be the potential therapies for OA. (frontiersin.org)
  • Treatment with pravastatin of stimulated human chondrocytes leads to significant down-regulation of selected MMP genes and a non-significant reduction in MMP enzyme activity. (springer.com)
  • Specific Aim 1: Define whether activation of the mTORC1 cascade by cyclic loading is required for mechanical regulation of chondrocyte proliferation and differentiation through Ihh. (lifespan.org)
  • Understanding in detail the important intracellular pathways activated by mechanical loading during chondrocyte differentiation, including the role of mTOR in mechanotransduction, will provide insight into molecular mechanisms underlying mechanical regulation of cartilage homeostasis, thereby benefiting cartilage tissue engineering and regenerative medicine. (lifespan.org)
  • Co-expression analysis of the miRNA and mRNA profiles showed that increasing stiffness resulted in up-regulation of miR-20a and down-regulation of decreased ankylosis protein homolog (ANKH) during inorganic phosphate-induced calcification in CEP chondrocytes. (unboundmedicine.com)
  • A significant negative correlation was observed between RUNX2 mRNA levels in OA chondrocytes and the percentage methylation of the CpG sites in the RUNX2 P1 promoter. (nature.com)
  • The mRNA and protein levels of cyclin D1, CDK4, CDK6, (p)Rb and P16 consistently demonstrated a reverse trend with the levels in the chondrocytes treated with nocodazole. (ingentaconnect.com)
  • The aim of this study is to assess the ability of pravastatin to modify matrix metalloproteinase (MMP) messenger RNA (mRNA) expression and enzyme activity in a culture of normal human chondrocytes stimulated by interleukin-1β. (springer.com)
  • Furthermore, overexpression of Klf4 or OSKM in three dimensional (3D) culture of equine chondrocytes resulted in a significant increase in Col2a1 mRNA levels relative to the controls (P (sigmaaldrich.com)
  • Finally, chondrocytes expressed prolactin mRNA (as revealed by RT-PCR) and they contained and released antiangiogenic N-terminal 16 kDa prolactin (detected by western blot and endothelial cell proliferation). (biologists.org)
  • These include oxidative stress, inadequacy of chondrocyte biosynthetic and growth responses, up-regulated chondrocyte cytokine-induced inflammation and matrix catabolism, pathologic cartilage matrix calcification, and increased chondrocyte death (necrosis or apoptosis). (mcponline.org)
  • Light micrograph of hyaline cartilage showing its chondrocytes and organelles , lacunae and matrix . (wikipedia.org)
  • The chondroblast is now a mature chondrocyte that is usually inactive but can still secrete and degrade the matrix, depending on conditions. (wikipedia.org)
  • The chondrocyte in cartilage matrix has rounded or polygonal structure. (wikipedia.org)
  • The low level of superoxide anions O 2- produced by chondrocytes in comparison with neutrophils may be involved in signal transduction and may be implicated in the structural and functional alterations of cartilage matrix observed in arthritis and osteoarthritis. (springer.com)
  • Fresh chondrocytes showed a high mitotic rate and abundant matrix was present up to 60 days of culture. (scielo.br)
  • Probable reason could be the deposition of iron in chondrocytes and matrix. (thefreedictionary.com)
  • Evidence linking chondrocyte lipid peroxidation to cartilage matrix protein degradation. (thefreedictionary.com)
  • We evidenced reduced chondrocyte nuclei, with hardly any lacunae present, surrounded by generous cartilaginous matrix with fibers (Figure 7). (thefreedictionary.com)
  • Pluripotent hESc, are established as feeder-free cultures4 prior to DDP being carried out in monolayer culture on a sequence of matrix protein-coated surfaces with a chemicallydefined medium sequentially supplemented with growth factors to directdifferentiation through developmental intermediate cell populations of primitive streak/mesendoderm (Stage 1), mesoderm (Stage 2) and then chondrocytes (Stage 3) (Figure 1). (stembook.org)
  • Articular cartilage is a highly specialised tissue composed of a mechanically competent matrix and a single cell population - the chondrocytes. (bl.uk)
  • Carvacrol also suppressed the protein expression levels of matrix metalloproteinase (MMP)‑3 and MMP‑13 in IL‑1β‑stimulated human OA chondrocytes. (spandidos-publications.com)
  • Moreover, we show that glucosamine hydrochloride prevents lipoprotein protein oxidation and inhibits malondialdehyde adduct formation in chondrocyte cell matrix, suggesting that it inhibits advanced lipoxidation reactions. (chiro.org)
  • Gille J, Behrens P, Schulz AP, Oheim R, Kienast B. Matrix-associated autologous chondrocyte implantation: a clinical follow-up at 15 years. (springer.com)
  • In this study, we found that matrix stiffness of CEP was positively correlated with the degree of IDD, and stiff matrix, which mimicked the severe degeneration of CEP, promoted inorganic phosphate-induced calcification in CEP chondrocytes. (unboundmedicine.com)
  • Moreover, it has been demonstrated that IL-1β causes chondrocytes to release matrix metalloproteinases (MMPs) leading to chondrocyte degradation [ 5 ]. (ijpsonline.com)
  • Here, we demonstrate that matrix metalloproteases (MMPs) produced and secreted by chondrocytes generate biologically functional 16K-prolactin from full-length prolactin. (biologists.org)
  • Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. (hindawi.com)
  • As possible outputs for this antioxidant deficiency, we found an increase of intracellular reactive oxygen species generation in OA chondrocytes and also verified an OA-dependent increase in the mitochondrial tumor necrosis factor-α receptor-associated protein 1 (TRAP1), a chaperone with a reported reactive oxygen species antagonist role. (mcponline.org)
  • However, the identity of the intracellular multi-protein complexes that transduce mechanical signals (mechanosomes) in chondrocytes is unclear. (lifespan.org)
  • We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. (portlandpress.com)
  • Hesperidin pretreatment decreased the formation of MDA and intracellular ROS, including chondrocyte apoptosis. (medscimonit.com)
  • The unbalanced production of catabolic and anabolic mediators by chondrocytes, the only cell type present in cartilage, determines cartilage degradation, which is the central pathological feature of OA. (wellnessresources.com)
  • Similar to other chondrocytes from hyaline cartilage tissues in other locations in the human body, NC undergo a process of cell de-differentiation during monolayer culture. (wikipedia.org)
  • Cellular perception and transduction of mechanical stress within cartilaginous tissues is an important modulator of chondrocyte function. (lifespan.org)
  • Activation of the MAPKs, ERK1, and ERK2, regulate Sox9 expression, which functions to suppress chondrocyte terminal differentiation and endochondral ossification. (wikipathways.org)
  • alpha]-Melanocyte-stimulating hormone ([alpha]-MSH) modulates human chondrocyte activation induced by proinflammatory cytokines. (thefreedictionary.com)
  • The exception occurs at tissue boundaries, for example the articular surfaces of joints, in which chondrocytes may be flattened or discoid. (wikipedia.org)
  • Nasal chondrocytes (NC) are present in the hyaline cartilage of the nasal septum, and in fact are the only cell type within the tissue. (wikipedia.org)
  • Articular chondrocytes have typically been the cell type used for cartilage tissue engineering strategies for articular cartilage repair. (wikipedia.org)
  • Trattnig, "Magnetic resonance observation of cartilage repair tissue (MOCART) forthe evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years, " European Journal of Radiology, vol. (thefreedictionary.com)
  • The only cell type present in mature cartilage is the chondrocyte, which is responsible for repairing cartilage tissue damaged by OA. (mcponline.org)
  • Autologous chondrocyte implantation is expected to promote the regeneration of TMJ cartilage tissue safely and effectively. (clinicaltrials.gov)
  • Autologous chondrocyte transplant is associated with morbidity of the cartilage sample removal, which needs intra-articular surgery, and the limited tissue sample for culture. (clinicaltrials.gov)
  • Adipose tissue yields more ASC than chondrocytes are obtained from cartilage, and liposuction is simple and with less adverse events than arthroscopy. (clinicaltrials.gov)
  • Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. (nih.gov)
  • Longitudinal growth of long bones occurs through endochondral ossification, which is accompanied by chondrocyte differentiation ( 1 ). (rupress.org)
  • Primary human chondrocytes isolated from individual donors. (promocell.com)
  • Bovine articular chondrocytes were encapsulated in the hydrogels and cultured for 14 days. (mdpi.com)
  • The formation of hyaline or hyaline-like cartilage may be induced by implanting autologous, cultured chondrocytes into the chondral or osteochondral defect. (nih.gov)
  • The independent contributions of the autologous cultured chondrocytes and other components of the therapy to outcome are unknown. (rxlist.com)
  • Autologous chondrocyte transplantation for the treatment of articular cartilage injuries has a durable outcome for as long as 11 years. (lu.se)
  • These highly hydrated gels allowed for cell proliferation of chondrocytes in three dimensions [Jayawarna, Ali, Jowitt, Miller, Saiani, Gough and Ulijn (2006) Adv. Mater. (biochemsoctrans.org)
  • The ability of these three new hydrogels to support cell proliferation of chondrocytes was confirmed for all three materials. (biochemsoctrans.org)
  • Biopsies from a lesser-weight bearing area are the credit of chondrocytes, which are isolated, expanded through cell culture, and implanted into articular cartilage defects beneath an autologous periosteal flap. (rxlist.com)
  • Chondrocytes had a more spread morphology in a low-viscosity gelatin solution than in a high-viscosity gelatin solution. (rsc.org)
  • The present study aimed to investigate the protective effects of carvacrol against inflammation in IL-1β-stimulated human chondrocytes, and the results demonstrated that carvacrol pretreatment inhibited IL-1β-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, and reduced the expression levels of iNOS, COX-2 and MMPs in human OA chondrocytes by suppressing the activation of the NF-κB signaling pathway. (spandidos-publications.com)
  • In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance. (portlandpress.com)
  • It can also regulate the function of chondrocytes. (mdpi.com)