Chondrogenesis: 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.Cartilage: 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.SOX9 Transcription Factor: 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.Chondrocytes: Polymorphic cells that form cartilage.SOXD Transcription Factors: 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.Collagen Type II: A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.Limb Buds: Distinct regions of mesenchymal outgrowth at both flanks of an embryo during the SOMITE period. Limb buds, covered by ECTODERM, give rise to forelimb, hindlimb, and eventual functional limb structures. Limb bud cultures are used to study CELL DIFFERENTIATION; ORGANOGENESIS; and MORPHOGENESIS.Extremities: The farthest or outermost projections of the body, such as the HAND and FOOT.Mesenchymal Stromal Cells: 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.Collagen Type X: A non-fibrillar collagen found primarily in terminally differentiated hypertrophic CHONDROCYTES. It is a homotrimer of three identical alpha1(X) subunits.Transforming Growth Factor beta3: A TGF-beta subtype that plays role in regulating epithelial-mesenchymal interaction during embryonic development. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta3 and TGF-beta3 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.High Mobility Group Proteins: A family of low-molecular weight, non-histone proteins found in chromatin.Chick Embryo: 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.Alcian Blue: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Mesoderm: The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.Aggrecans: 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.Periosteum: Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.Osteogenesis: The process of bone formation. Histogenesis of bone including ossification.Bone Morphogenetic Protein 2: A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.Bone Morphogenetic Proteins: 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.Growth Plate: The area between the EPIPHYSIS and the DIAPHYSIS within which bone growth occurs.Growth Differentiation Factor 5: A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.Tissue Engineering: 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.Gene Expression Regulation, Developmental: 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.Cartilage, Articular: 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.Bone Development: 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.Glycosaminoglycans: 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.Cells, Cultured: 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.Metatarsal Bones: The five long bones of the METATARSUS, articulating with the TARSAL BONES proximally and the PHALANGES OF TOES distally.Extracellular Matrix Proteins: 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).Hydrogels: 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)Collagen: 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).Tissue Scaffolds: 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.Extracellular Matrix: 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.Bone Morphogenetic Protein 6: A bone morphogenetic protein that is a potent inducer of BONE formation. It plays additional roles in regulating CELL DIFFERENTIATION of non-osteoblastic cell types and epithelial-mesenchymal interactions.Transforming Growth Factor beta: 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.Mandible: The largest and strongest bone of the FACE constituting the lower jaw. It supports the lower teeth.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Bone and Bones: 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.In Situ Hybridization: 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.Elaeagnaceae: A plant family of the order Rhamnales, subclass Rosidae class Magnoliopsida. The plants have a characteristic silvery or rusty-colored sheen, caused by tiny distinctive scales. Flowers have a tubular structure of four sepals. Root nodules host the Frankia (ACTINOMYCETES) nitrogen-fixing symbionts.Bone Morphogenetic Protein 4: A bone morphogenetic protein that is a potent inducer of bone formation. It also functions as a regulator of MESODERM formation during EMBRYONIC DEVELOPMENT.Skull: The SKELETON of the HEAD including the FACIAL BONES and the bones enclosing the BRAIN.Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type.Hedgehog Proteins: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Versicans: HYALURONAN-containing proteoglycans found in the EXTRACELLULAR MATRIX of a variety of tissues and organs. Several versican isoforms exist due to multiple ALTERNATIVE SPLICING of the versican MESSENGER RNA.Polyhydroxyethyl Methacrylate: A biocompatible, hydrophilic, inert gel that is permeable to tissue fluids. It is used as an embedding medium for microscopy, as a coating for implants and prostheses, for contact lenses, as microspheres in adsorption research, etc.Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Reverse Transcriptase Polymerase Chain Reaction: 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.Transforming Growth Factor beta1: 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.Core Binding Factor Alpha 1 Subunit: 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.Hyaline Cartilage: 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.Signal Transduction: 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.Bone Morphogenetic Protein Receptors, Type I: A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS.Forelimb: A front limb of a quadruped. (The Random House College Dictionary, 1980)Collagen Type IX: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Matrilin Proteins: 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.Bony Callus: The bony deposit formed between and around the broken ends of BONE FRACTURES during normal healing.SepharoseBranchial Region: A region, of SOMITE development period, that contains a number of paired arches, each with a mesodermal core lined by ectoderm and endoderm on the two sides. In lower aquatic vertebrates, branchial arches develop into GILLS. In higher vertebrates, the arches forms outpouchings and develop into structures of the head and neck. Separating the arches are the branchial clefts or grooves.Bone Morphogenetic Protein Receptors: A family of CELL SURFACE RECEPTORS that bind BONE MORPHOGENETIC PROTEINS. They are PROTEIN-SERINE-THREONINE KINASES that mediate SIGNAL TRANSDUCTION PATHWAYS through SMAD PROTEINS.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Limb Deformities, Congenital: Congenital structural deformities of the upper and lower extremities collectively or unspecified.Culture Techniques: Methods of maintaining or growing biological materials in controlled laboratory conditions. These include the cultures of CELLS; TISSUES; organs; or embryo in vitro. Both animal and plant tissues may be cultured by a variety of methods. Cultures may derive from normal or abnormal tissues, and consist of a single cell type or mixed cell types.Hexuronic Acids: 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.Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner SYNOVIAL MEMBRANE.RNA, Messenger: 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.Hyaluronic Acid: 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.Glucuronic Acid: 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.Growth Differentiation Factor 10: A growth differentiation factor that is closely-related in structure to BONE MORPHOGENETIC PROTEIN 3. Growth differentiation factor 10 is found at high levels in BONE, however it plays an additional roles in regulating EMBRYONIC DEVELOPMENT.Toes: Any one of five terminal digits of the vertebrate FOOT.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Gene Expression Regulation: 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.Antlers: The horn of an animal of the deer family, typically present only in the male. It differs from the HORNS of other animals in being a solid, generally branched bony outgrowth that is shed and renewed annually. The word antler comes from the Latin anteocularis, ante (before) + oculus (eye). (From Webster, 3d ed)Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Lectins, C-Type: 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.Neural Crest: The two longitudinal ridges along the PRIMITIVE STREAK appearing near the end of GASTRULATION during development of nervous system (NEURULATION). The ridges are formed by folding of NEURAL PLATE. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the NEURAL TUBE.Cell Enlargement: Growth processes that result in an increase in CELL SIZE.Osteochondrodysplasias: Abnormal development of cartilage and bone.Ectoderm: The outer of the three germ layers of an embryo.Hindlimb: Either of two extremities of four-footed non-primate land animals. It usually consists of a FEMUR; TIBIA; and FIBULA; tarsals; METATARSALS; and TOES. (From Storer et al., General Zoology, 6th ed, p73)Morphogenesis: The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.WingChondroitin: A mucopolysaccharide constituent of chondrin. (Grant & Hackh's Chemical Dictionary, 5th ed)Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.Cellular Microenvironment: Local surroundings with which cells interact by processing various chemical and physical signals, and by contributing their own effects to this environment.Tissue Culture Techniques: 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.Wnt Proteins: Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Alginates: Salts of alginic acid that are extracted from marine kelp and used to make dental impressions and as absorbent material for surgical dressings.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Hypertrophy: 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).Receptor, Fibroblast Growth Factor, Type 3: 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.Arthroplasty, Subchondral: Surgical techniques used to correct or augment healing of chondral defects in the joints (CARTILAGE, ARTICULAR). These include abrasion, drilling, and microfracture of the subchondral bone to enhance chondral resurfacing via autografts, allografts, or cell transplantation.Cartilage Diseases: Pathological processes involving the chondral tissue (CARTILAGE).Ear: The hearing and equilibrium system of the body. It consists of three parts: the EXTERNAL EAR, the MIDDLE EAR, and the INNER EAR. Sound waves are transmitted through this organ where vibration is transduced to nerve signals that pass through the ACOUSTIC NERVE to the CENTRAL NERVOUS SYSTEM. The inner ear also contains the vestibular organ that maintains equilibrium by transducing signals to the VESTIBULAR NERVE.Guided Tissue Regeneration: Procedures for enhancing and directing tissue repair and renewal processes, such as BONE REGENERATION; NERVE REGENERATION; etc. They involve surgically implanting growth conducive tracks or conduits (TISSUE SCAFFOLDING) at the damaged site to stimulate and control the location of cell repopulation. The tracks or conduits are made from synthetic and/or natural materials and may include support cells and induction factors for CELL GROWTH PROCESSES; or CELL MIGRATION.Sulfates: Inorganic salts of sulfuric acid.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Embryonic Induction: The complex processes of initiating CELL DIFFERENTIATION in the embryo. The precise regulation by cell interactions leads to diversity of cell types and specific pattern of organization (EMBRYOGENESIS).Comb and Wattles: Fleshy and reddish outgrowth of skin tissue found on top of the head, attached to the sides of the head, and hanging from the mandible of birds such as turkeys and chickens.Fibroblast Growth Factors: A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.Collagen Type XI: A fibrillar collagen found primarily in interstitial CARTILAGE. Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits.Fracture Healing: The physiological restoration of bone tissue and function after a fracture. It includes BONY CALLUS formation and normal replacement of bone tissue.Bone Matrix: Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.Adipogenesis: The differentiation of pre-adipocytes into mature ADIPOCYTES.Notochord: A cartilaginous rod of mesodermal cells at the dorsal midline of all CHORDATE embryos. In lower vertebrates, notochord is the backbone of support. In the higher vertebrates, notochord is a transient structure, and segments of the vertebral column will develop around it. Notochord is also a source of midline signals that pattern surrounding tissues including the NEURAL TUBE development.Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee.Bone Morphogenetic Protein 7: A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.Oligonucleotides, Antisense: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.Calcification, Physiologic: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.Parathyroid Hormone-Related Protein: 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.Achondroplasia: 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)Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

Mechanisms of GDF-5 action during skeletal development. (1/992)

Mutations in GDF-5, a member of the TGF-beta superfamily, result in the autosomal recessive syndromes brachypod (bp) in mice and Hunter-Thompson and Grebe-type chondrodysplasias in humans. These syndromes are all characterised by the shortening of the appendicular skeleton and loss or abnormal development of some joints. To investigate how GDF-5 controls skeletogenesis, we overexpressed GDF-5 during chick limb development using the retrovirus, RCASBP. This resulted in up to a 37.5% increase in length of the skeletal elements, which was predominantly due to an increase in the number of chondrocytes. By injecting virus at different stages of development, we show that GDF-5 can increase both the size of the early cartilage condensation and the later developing skeletal element. Using in vitro micromass cultures as a model system to study the early steps of chondrogenesis, we show that GDF-5 increases chondrogenesis in a dose-dependent manner. We did not detect changes in proliferation. However, cell suspension cultures showed that GDF-5 might act at these stages by increasing cell adhesion, a critical determinant of early chondrogenesis. In contrast, pulse labelling experiments of GDF-5-infected limbs showed that at later stages of skeletal development GDF-5 can increase proliferation of chondrocytes. Thus, here we show two mechanisms of how GDF-5 may control different stages of skeletogenesis. Finally, our data show that levels of GDF-5 expression/activity are important in controlling the size of skeletal elements and provides a possible explanation for the variation in the severity of skeletal defects resulting from mutations in GDF-5.  (+info)

gas2 is a multifunctional gene involved in the regulation of apoptosis and chondrogenesis in the developing mouse limb. (2/992)

The growth-arrest-specific 2 (gas2) gene was initially identified on account of its high level of expression in murine fibroblasts under growth arrest conditions, followed by downregulation upon reentry into the cell cycle (Schneider et al., Cell 54, 787-793, 1988). In this study, the expression patterns of the gas2 gene and the Gas2 peptide were established in the developing limbs of 11.5- to 14. 5-day mouse embryos. It was found that gas2 was expressed in the interdigital tissues, the chondrogenic regions, and the myogenic regions. Low-density limb culture and Brdu incorporation assays revealed that gas2 might play an important role in regulating chondrocyte proliferation and differentiation. Moreover, it might play a similar role during limb myogenesis. In addition to chondrogenesis and myogeneis, gas2 is involved in the execution of the apoptotic program in hindlimb interdigital tissues-by acting as a death substrate for caspase enzymes. TUNEL analysis demonstrated that the interdigital tissues underwent apoptosis between 13.5 and 15.5 days. Exactly at these time points, the C-terminal domain of the Gas2 peptide was cleaved as revealed by Western blot analysis. Moreover, pro-caspase-3 (an enzyme that can process Gas2) was cleaved into its active form in the interdigital tissues. The addition of zVAD-fmk, a caspase enzyme inhibitor, to 12.5-day-old hindlimbs maintained in organ culture revealed that the treatment inhibited interdigital cell death. This inhibition correlated with the absence of the Gas2 peptide and pro-caspase-3 cleavage. The data suggest that Gas2 might be involved in the execution of the apoptotic process.  (+info)

Expression of tissue transglutaminase in the developing chicken limb is associated both with apoptosis and endochondral ossification. (3/992)

The cross-linking enzyme tissue transglutaminase (tTG) participates in a variety of cellular functions. To assess its contribution to extracellular and intracellular processes during development we cloned the cDNA for chicken heart tissue transglutaminase and localized the sites of transglutaminase expression by in situ hybridization and immunohistochemistry. Compared with the chicken red blood cell transglutaminase cDNA, the heart cDNA encodes a transglutaminase with an amino-terminal truncation. The truncated enzyme retains full catalytic activity and is GTP-inhibitable. Tissue transglutaminase expression was observed in developmentally transient structures in embryonic chicken limb at day 7.5 of incubation suggesting that its expression is dynamically regulated during limb morphogenesis. The major morphogenetic events of the limb associated with transglutaminase expression were cartilage maturation during skeletal development, interdigital apoptosis, and differentiation of skeletal muscle. Maturation of the cartilage during endochondral ossification was characterized by intra- and extracellular transglutaminase accumulation in the zone of hypertrophic chondrocytes. Only intracellular enzyme could be detected in mesenchymal cells of the prospective joints, in apoptotic cells of the interdigital web, and in skeletal muscle myoblasts. An apparently constitutive expression of tissue transglutaminase was found in vascular endothelial cells corresponding to the adult expression pattern. The dynamic pattern of transglutaminase expression during morphogenesis suggests that tissue remodeling is a major trigger for transglutaminase induction.  (+info)

Alcohol promotes in vitro chondrogenesis in embryonic facial mesenchyme. (4/992)

Ethanol is a well-recognized teratogen in vertebrates that can perturb the development of the facial primordia and various other embryonic structures. However,the mechanisms underlying alcohol's effects on embryogenesis are currently unclear. Recent evidence suggests that the cranial neural crest, which forms the entire facial skeleton, may be a particularly sensitive target of ethanol teratogenicity. In the present study we have examined the influence of in vitro ethanol exposure on cartilage differentiation in micromass cultures of mesenchymal cells isolated from the various facial primordia (maxillary, mandibular, frontonasal, and hyoid processes) of the stage 24 chick embryo. In all four populations of facial mesenchyme, exposure to 1-1.5% ethanol promoted marked increases in Alcian blue-positive cartilage matrix formation, a rise in 35SO4 accumulation into matrix glycosaminoglycans, and enhanced expression of cartilage-characteristic type II collagen and aggrecan gene transcripts. In frontonasal and mandibular mesenchyme cultures, which undergo extensive spontaneous cartilage formation, ethanol treatment quantitatively elevated both matrix production and cartilage-specific gene transcript expression. In cultures of maxillary process and hyoid arch mesenchyme, which form little or no cartilage spontaneously, ethanol exposure induced the formation of chondrogenic cell aggregates and the appearance of aggrecan and type II collagen mRNAs. These actions were not restricted to ethanol, since tertiary butanol treatment also enhanced cartilage differentiation in facial mesenchyme cultures. Our findings demonstrate a potent stimulatory effect of alcohol on the differentiation of prechondrogenic mesenchyme of the facial primordia. Further analysis of this phenomenon might yield insight into the developmental mechanisms underlying the facial dysmorphologies associated with embryonic ethanol exposure.  (+info)

Interaction of Ihh and BMP/Noggin signaling during cartilage differentiation. (5/992)

Bone morphogenetic proteins (BMPs) have been implicated in regulating multiple stages of bone development. Recently it has been shown that constitutive activation of the BMP receptor-IA blocks chondrocyte differentiation in a similar manner as misexpression of Indian hedgehog. In this paper we analyze the role of BMPs as possible mediators of Indian hedgehog signaling and use Noggin misexpression to gain insight into additional roles of BMPs during cartilage differentiation. We show by comparative analysis of BMP and Ihh expression domains that the borders of Indian hedgehog expression in the chondrocytes are reflected in changes of the expression level of several BMP genes in the adjacent perichondrium. We further demonstrate that misexpression of Indian hedgehog appears to directly upregulate BMP2 and BMP4 expression, independent of the differentiation state of the flanking chondrocytes. In contrast, changes in BMP5 and BMP7 expression in the perichondrium correspond to altered differentiation states of the flanking chondrocytes. In addition, Noggin and Chordin, which are both expressed in the developing cartilage elements, also change their expression pattern after Ihh misexpression. Finally, we use retroviral misexpression of Noggin, a potent antagonist of BMP signaling, to gain insight into additional roles of BMP signaling during cartilage differentiation. We find that BMP signaling is necessary for the growth and differentiation of the cartilage elements. In addition, this analysis revealed that the members of the BMP/Noggin signaling pathway are linked in a complex autoregulatory network.  (+info)

N-CAM is not required for initiation of secondary chondrogenesis: the role of N-CAM in skeletal condensation and differentiation. (6/992)

Condensation precedes chondrogenic differentiation during development of primary cartilage. While neural cell adhesion molecule (N-CAM) enhances condensation, it is unclear whether N-CAM is also required for initiation of chondrogenic differentiation. In this study, the role of N-CAM in secondary chondrogenesis from periosteal cells of the quadratojugal (QJ) from embryonic chicks was studied using several in vitro approaches. The QJ is a membrane bone and so is not preceded by cartilage formation during development. However, QJ periosteal cells can differentiate into chondrocytes to form secondary cartilage in vivo. When QJ periosteal cells were enzymatically released and plated in low density monolayer, clonal or agarose cultures, chondrogenesis was initiated in the absence of N-CAM expression. Furthermore, overexpression of the N-CAM gene in periosteal cells in monolayer culture significantly reduced the number of chondrocyte colonies, suggesting that N-CAM inhibits secondary chondrogenesis. In contrast, and consistent with expression in vivo, N-CAM is expressed during osteogenesis from QJ periosteal cells and mandibular mesenchyme in vitro. These results are discussed in relation to the role of N-CAM in osteogenesis and in primary and secondary condensation.  (+info)

Dual role of the basic helix-loop-helix transcription factor scleraxis in mesoderm formation and chondrogenesis during mouse embryogenesis. (7/992)

Scleraxis is a basic helix-loop-helix (bHLH) transcription factor shown previously to be expressed in developing chondrogenic cell lineages during embryogenesis. To investigate its function in embryonic development, we produced scleraxis-null mice by gene targeting. Homozygous mutant embryos developed normally until the early egg cylinder stage (embryonic day 6.0), when they became growth-arrested and failed to gastrulate. Consistent with this early embryonic phenotype, scleraxis was found to be expressed throughout the embryo at the time of gastrulation before becoming restricted to chondrogenic precursor cells at embryonic day 9.5. At the time of developmental arrest, scleraxis-null embryos consisted of ectodermal and primitive endodermal cell layers, but lacked a primitive streak or recognizable mesoderm. Analysis of molecular markers of the three embryonic germ layers confirmed that scleraxis mutant embryos were unable to form mesoderm. By generating chimeric embryos, using lacZ-marked scleraxis-null and wild-type embryonic stem cells, we examined the ability of mutant cells to contribute to regions of the embryo beyond the time of lethality of homozygous mutants. Scleraxis-null cells were specifically excluded from the sclerotomal compartment of somites, which gives rise to the axial skeleton, and from developing ribs, but were able to contribute to most other regions of the embryo, including mesoderm-derived tissues. These results reveal an essential early role for scleraxis in mesoderm formation, as well as a later role in formation of somite-derived chondrogenic lineages, and suggest that scleraxis target genes mediate these processes.  (+info)

The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb. (8/992)

In this study, we have analyzed the expression and function of Gremlin in the developing avian limb. Gremlin is a member of the DAN family of BMP antagonists highly conserved through evolution able to bind and block BMP2, BMP4 and BMP7. At early stages of development, gremlin is expressed in the dorsal and ventral mesoderm in a pattern complementary to that of bmp2, bmp4 and bmp7. The maintenance of gremlin expression at these stages is under the control of the AER, ZPA, and BMPs. Exogenous administration of recombinant Gremlin indicates that this protein is involved in the control of limb outgrowth. This function appears to be mediated by the neutralization of BMP function to maintain an active AER, to restrict the extension of the areas of programmed cell death and to confine chondrogenesis to the central core mesenchyme of the bud. At the stages of digit formation, gremlin is expressed in the proximal boundary of the interdigital mesoderm of the chick autopod. The anti-apoptotic influence of exogenous Gremlin, which results in the formation of soft tissue syndactyly in the chick, together with the expression of gremlin in the duck interdigital webs, indicates that Gremlin regulates the regression of the interdigital tissue. At later stages of limb development, gremlin is expressed in association with the differentiating skeletal pieces, muscles and the feather buds. The different expression of Gremlin in relation with other BMP antagonists present in the limb bud, such as Noggin, Chordin and Follistatin indicates that the functions of BMPs are regulated specifically by the different BMP antagonists, acting in a complementary fashion rather than being redundant signals.  (+info)

Yang, Z., Sui, L., Toh, W.S., Cao, T., Lee, E.H. (2009). Stage-dependent effect of TGF-1 on chondrogenic differentiation of human embryonic stem cells. Stem Cells and Development 18 (6) : 929-940. [email protected] Repository. https://doi.org/10.1089/scd. ...
We have recently identified Dlkl/FA1 as a novel surface marker for chondroprogenitor cells during embryonic chondrogenesis and demonstrated the Akt pathway-dependent inhibition of insulin induced in vitro chondrogenesis by Dlk1/FA1 [21, 22]. However, the mechanisms by which Dlk1 is regulated and its interaction with other signaling pathways during chondrogenic differentiation are not well known. In this study, we have identified Dlk1 as a novel downstream target of the TGF-β signaling pathway that mediates its function by promoting early chondrogenesis. Additionally, we observed altered Smad2 phosphorylation with Dlk1/FA1 overexpression suggesting that Dlk1/FA1 inhibits activation of TGF-β signaling pathway.. We used mouse embryonic limb bud culture as an in vitro system that spontaneously differentiates in culture without any exogenous chondrogenic inducers and recapitulates the sequential stages of chondrogenesis from condensing mesenchyme to matrix mineralization [24, 39, 40]. The ...
Results Mesodermal markers increased in EB while undifferentiated ES markers disappeared. After 21 days of chondrogenic culture in micromass pellets, GAG analysis showed that proteoglycan production was significantly greater in chondrogenic pellets than in undifferentiated hiPSCs and EBs. Safranin-O staining demonstrated that the cells in chondrogenic pellets took on the appearance of immature chondrocytes and secreted extracellular matrix. The chondrogenic marker gene and protein expression increased after 21days of pellet culture. The chondrogenic pellets derived from hiPS cells have very low expression of hypertrophic or osteogenic markers.. Also, hiPS cells underwent good chondrogenic differentiation in PLGA scaffold or alginate gel as well. When hiPS cells in either pellet state or in alginate hydrogel were implanted in the osteochondral defects created on the patellar groove of immunosuppressed rats, the defects implanted with chondro-induced hiPS cells showed a significantly better ...
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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
Epigenetic changes (i.e., chromatin modifications) occur during chondrogenesis and in osteoarthritis (OA). We investigated the effect of H3K27me3 demethylase inhibition on chondrogenesis and assessed its utility in cartilage tissue engineering and in understanding cartilage destruction in OA. We used a high-content screen to assess the effect of epigenetic modifying compounds on collagen output during chondrogenesis of monolayer human mesenchymal stem cells (MSCs). The impact of GSK-J4 on gene expression, glycosaminoglycan output and collagen formation during differentiation of MSCs into cartilage discs was investigated. Expression of lysine (K)-specific demethylase 6A (UTX) and Jumonji domain-containing 3 (JMJD3), the HEK27Me3 demethylases targeted by GSK-J4, was measured in damaged and undamaged cartilage from patients with OA. The impact of GSK-J4 on ex vivo cartilage destruction and expression of OA-related genes in human articular chondrocytes (HACs) was assessed. H3K27Me3 demethylase regulation of
BACKGROUND: Epigenetic changes (i.e., chromatin modifications) occur during chondrogenesis and in osteoarthritis (OA). We investigated the effect of H3K27me3 demethylase inhibition on chondrogenesis and assessed its utility in cartilage tissue engineering and in understanding cartilage destruction in OA. METHODS: We used a high-content screen to assess the effect of epigenetic modifying compounds on collagen output during chondrogenesis of monolayer human mesenchymal stem cells (MSCs). The impact of GSK-J4 on gene expression, glycosaminoglycan output and collagen formation during differentiation of MSCs into cartilage discs was investigated. Expression of lysine (K)-specific demethylase 6A (UTX) and Jumonji domain-containing 3 (JMJD3), the HEK27Me3 demethylases targeted by GSK-J4, was measured in damaged and undamaged cartilage from patients with OA. The impact of GSK-J4 on ex vivo cartilage destruction and expression of OA-related genes in human articular chondrocytes (HACs) was assessed. H3K27Me3
To investigate underlying mechanism of chondrogenic hypertrophy, we need proper in vitro hypertrophic model of mesenchymal stem cells (MSCs). This protocol describes our defined method for induction of in vitro chondrogenic hypertrophy of human umbilical cord blood-derived MSCs (hUCB-MSCs). By adding thyroid hormone (T3; triiodothyronine) and minimum osteogenic-inducing factors to culture medium, we could induce hypertrophy of hUCB-MSCs in vitro. Hypertrophic induction was validated using immunohistochemical analysis, Western blotting and reverse transcriptase polymerase chain reaction.
Abstract: A novel collagen sponge that can protect cell leakage during cell seeding was developed by wrapping all the surfaces except the upside of a collagen sponge with membrane that has pores smaller than cell. The collagen sponge was used for three-dimensional culture of human bone marrow-derived mesenchymal stem cells (MSCs). The cells adhered to the collagen, and proliferated to fill the spaces in the sponge. The cell seeding efficiency was higher than 95%. The MSCs cultured in the collagen sponge in the chondrogenic induction medium supplemented with TGF-β3 and BMP6 expressed genes encoding type II collagen, SOX9 and aggrecan. HE staining indicated the round morphology of differentiated cells and the extracelluler matrices were positively stained by safranin O and toluidine blue. Type II collagen and cartilage proteoglycan were detected by immunostaining with anti-type II collagen and anti-cartilage proteoglycan. These results suggest the chondrogenic differentiation of MSCs. The ...
Murine micromass versions have been extensively applied to study chondrogenesis and osteogenesis to elucidate pathways of endochondral bone formation. Apart from lineage-specific marker genes, pluripotency factors (and model systems have been AMD 070 established and validated to study chondrogenesis and early phases of matrix calcification. Since the initial condensation of mesenchymal cells is usually a prerequisite to their subsequent difference, by mimicking these circumstances was first described by co-workers and Ahrens [5]. In these high thickness cell civilizations (HDC), the natural capacity of poultry arm or leg bud-derived chondroprogenitor mesenchymal cells to automatically differentiate to chondroblasts and chondrocytes on times 2 and 3 AMD 070 of culturing is certainly used; a well-detectable quantity of hyaline cartilage extracellular matrix (ECM) is certainly created by time 6. A significant benefit of this technique over others is certainly its cost-effectiveness and the ...
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In this work, it was hypothesized that co-cultures of articular chondrocytes (ACs) and mesenchymal stem cells (MSCs) would exhibit enhanced sensitivity to chondrogenic stimuli, such as TGF-β3, and would require a reduced concentration of TGF-β3 to achieve an equivalent level of chondrogenesis compared to monocultures of each cell type. Furthermore, it was hypothesized that compared to monocultures, the chondrogenic phenotype of AC/MSC co-cultures would be more stable upon the removal of TGF-β3 from the culture medium. These hypotheses were investigated by culturing ACs and MSCs alone and in a 1:3 ratio on electrospun poly(ɛ-caprolactone) scaffolds. All cell populations were cultured for two weeks with 0, 1, 3, or 10 ng/ml of TGF-β3. After two weeks growth factor supplementation was removed, and the constructs were cultured for two additional weeks. Cell proliferation, extracellular matrix production, and chondrogenic gene expression were evaluated after two and four weeks. The results ...
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Objectives: Osteoarthritis (OA) is a joint disease involving progressive and degenerative changes to articular cartilage that greatly affects the adult population. Autologous chondrocyte implantation (ACI) has been used to treat focal early OA defects, although there are negative long-term outcomes due to poor graft integration and the presence of inflammatory factors Bone marrow derived mesenchymal stem cells (MSCs) are an alternative cell type for cell-based treatments due to their chondrogenic capacity. However, MSC chondrogenesis leads to bone formation upon in vivo implantation. In vivo, chondrocytes reside under an oxygen tension between 2-7% oxygen or physioxia. Previous studies have demonstrated that physioxia enhances MSC chondrogenesis with reduced hypertrophic marker (collagen X and MMP13) expression compared to hyperoxia (20% oxygen). The present investigation sought to observe whether implantation of physioxic preconditioned MSCs improves cartilage repair in an early OA defect model ...
Objective. Mature articular cartilage is vulnerable to injuries and disease processes that cause irreversible tissue damage because of its limited capacity for self-repair. Umbilical cord blood is a source of mesenchymal stem cells, which can give rise to cells of different lineages, including cartilage, bone, and fat. Cellular condensation is a required step in the initiation of mesenchymal chondrogenesis. We attempted to differentiate cells from umbilical cord blood into chondrocytes with insulin-like growth factor 1 (IGF-1) and transforming growth factor-beta 3 (TGF-beta 3). Methods. Cells were grown in high density micromass and monolayer culture systems and then evaluated for expression of type 11 collagen, aggrecan, and Sox9. Umbilical cord blood from 130 patients was harvested. Results. Expression of type II collagen, aggrecan, and Sox9 was detected after 14 days in TGF-beta 3- and IGF-1-stimulated cells in both types of culture (monolayer and micromass). On Day 21 in the micromass ...
In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first step of endochondral ossification. However, the molecular pathways leading to such phenotype are still unknown. Using protein immunodetection and histological techniques comparing transgenic mice to controls, we show here that the persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the differentiation cascade, such as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9 and Wnt5a. These data confirm the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also show a selective effect of Hoxa2 on endochondral ossification processes since Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively. Since
Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral...
Hanamura, H and Urist, M R., "Osteogenesis and chondrogenesis in transplants of dunn and ridgway osteosarcoma cell cultures." (1978). Subject Strain Bibliography 1978. 4164 ...
以人類疾病動物模式探討微環境對幹細胞命運之影響--探討玻尿酸與軟骨素在聚乳酸立體培養架構中之軟骨分化的影響The effects of hyaluronic acid and chondrotin on chondrogenesis in 3D-PLGA scaffold (國科會), 2011.8- ...
Fully tested and working Micromass GCT with EI source, Agilent 6890N GC with split/splitless, CTC HTS modified/Combi Pal with Liquid injection only(l
TY - JOUR. T1 - Fibrin and poly(lactic-co-glycolic acid) hybrid scaffold promotes early chondrogenesis of articular chondrocytes. T2 - An in vitro study. AU - ShaBan, Munirah. AU - Kim, Soon Hee. AU - Idrus, Ruszymah. AU - Khang, Gilson. PY - 2008. Y1 - 2008. N2 - Background. Synthetic- and naturally derived- biodegradable polymers have been widely used to construct scaffolds for cartilage tissue engineering. Poly(lactic-co-glycolic acid) (PLGA) are bioresorbable and biocompatible, rendering them as a promising tool for clinical application. To minimize cells lost during the seeding procedure, we used the natural polymer fibrin to immobilize cells and to provide homogenous cells distribution in PLGA scaffolds. We evaluated in vitro chondrogenesis of rabbit articular chondrocytes in PLGA scaffolds using fibrin as cell transplantation matrix. Methods. PLGA scaffolds were soaked in chondrocytes-fibrin suspension (1 × 106cells/ scaffold) and polymerized by dropping thrombin-calcium chloride (CaCl ...
We have used a disc-shaped self-gelling alginate hydrogel as a scaffold for in vitro chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. The comparison of monolayer cells and alginate embedded cells with or without differentiation medium allowed us to perform a detailed kinetic study of the expression of a range of genes and proteins known to be involved in chondrogenesis, using real-time polymerase chain reaction, fluorescence immunohistochemistry, and glycosaminoglycan measurement in the supernatant. mRNA encoding type II collagen (COL2), COL10, aggrecan, and SOX5, 6, and 9 were greatly elevated already at day 7, whereas COL1 and versican mRNA were gradually reduced. COL2 and aggrecan were dispersed throughout the extracellular matrix at day 21, whereas COL10 distribution was mainly intra/pericellular. COL1 seemed to be produced by only some of the cells. SOX proteins were predominantly localized in the nuclei. Then, using microarray analysis, we identified a signature
TY - JOUR. T1 - In vitro chondrogenesis of bone marrow-derived mesenchymal stem cells in a photopolymerizing hydrogel. AU - Williams, Christopher G.. AU - Kim, Tae Kyun. AU - Taboas, Anya. AU - Malik, Athar. AU - Manson, Paul. AU - Elisseeff, Jennifer Hartt. PY - 2003/8. Y1 - 2003/8. N2 - Mesenchymal stem cells (MSCS) from skeletally mature goats were encapsulated in a photopolymerizing poly(ethylene glycol)-based hydrogel and cultured with or without transforming growth factor β1 (TGF) to study the potential for chondrogenesis in a hydrogel scaffold system amenable to minimally invasive implantation. Chondrogenic differentiation was evaluated by histological, biochemical, and RNA analyses for the expression of cartilage extracellular matrix components. The two control groups studied were MSCs cultured in monolayer and MSCs encapsulated in the hydrogel and cultured for 6 weeks in chondrogenic medium without TGF-β1 (6wk-TGF). The three experimental time points for encapsulated cells studied ...
Human embryonic stem cells (hESCs) have the potential to offer a virtually unlimited source of chondrogenic cells for use in cartilage repair and regeneration. We have recently shown that expandable chondrogenic cells can be derived from hESCs under selective growth factor-responsive conditions. In this study, we explore the potential of these hESC-derived chondrogenic cells to produce an extracellular matrix (ECM)-enriched cartilaginous tissue construct when cultured in hyaluronic acid (HA)-based hydrogel, and further investigated the long-term reparative ability of the resulting hESC-derived chondrogenic cell-engineered cartilage (HCCEC) in an osteochondral defect model. We hypothesized that HCCEC can provide a functional template capable of undergoing orderly remodeling during the repair of critical-sized osteochondral defects (1.5 mm in diameter, 1 mm depth into the subchondral bone) in a rat model. In the process of repair, we observed an orderly spatial-temporal remodeling of HCCEC over 12 ...
TY - JOUR. T1 - Induction of chondrogenesis. T2 - Requirement for synergistic interaction of basic fibroblast growth factor and transforming growth factor-beta. AU - Frenz, Dorothy A.. AU - Liu, Wei. AU - Williams, James D.. AU - Hatcher, Victor Bernard. AU - Galinovic-Schwartz, Vera. AU - Flanders, Kathleen C.. AU - Van De Water, Thomas R.. PY - 1994/2. Y1 - 1994/2. N2 - Interactions between the epithelial anlage of the developing mouse inner ear and its associated periotic mesenchyme control the differentiation of the cartilaginous otic capsule. Transforming growth factor-beta1 (TGF-β1) is a naturally occurring signal peptide that is present in these tissues at times of active differentiation and morphogenesis. Previous studies have shown that TGF-β1 alone is not a sufficient stimulus to initiate chondrogenesis in cultured periotic mesenchyme. In this study, we provide evidence that basic fibroblast growth factor (bFGF) can elicit a specific but limited chondrogenic response in cultured ...
Human mesenchymal stem cells (hMSCs) show promise for bone and cartilage regeneration. Our previous studies demonstrated that hMSCs with periodic mild heating had enhanced osteogenic and chondrogenic differentiation with significantly upregulated heat shock protein 70 (HSP70). However, the role of H …
In chapter 1, we sought a proof of principle to confirm that the blocking of angiogenesis does indeed improve cartilage formation when using genetically-modified nasal chondrocytes (NCs) or antiangiogenic peptides associated with NCs. For this purpose, NCs were genetically-modified to express mouse soluble VEGF receptor-2 (sFlk-1) or were associated with an antiangiogenic peptide in order to have their chondrogenic capacity assessed in vitro and in vivo. Improved cartilage regeneration could be observed after in vivo implantation of NCs in an ectopic nude mouse model. Whereas the anti-angiogenic approaches did not improve chondrogenesis in vitro, frank chondrogenesis occured in vivo only in the constructs generated by NCs expressing sFlk-1 or treated with the peptide. Blood vessel ingrowth was significantly hampered in the anti-angiogenic experimental groups when compared with naïve NCs, which correlated with chondrogenis improvement. Strikingly, the anti-angiogenic effect was even more evident ...
Although BMSC-based therapy is one of the most front-line technologies for cartilage repair, it is still a big challenge to attain ideal niches for BMSC chondrogenic differentiation. In this study, we developed hyaluronate and chondroitin sulfate derivatives to prepare covalently crosslinked polysaccharide h 2017 Journal of Materials Chemistry B HOT Papers
TGF-β3 is enzymatically immobilized by transglutaminase-2 action to poly(L-lactic acid) microparticles coated with collagen II. Microparticles are then encapsulated with stem cells inside liquified spherical compartments enfolded with a permselective shell through layer-by-layer adsorption. Magnetic nanoparticles are electrostatically bound to the multilayered shell, conferring magnetic-response ability. The goal of this study is to engineer a closed environment inside which encapsulated stem cells would undergo a self-regulated chondrogenesis. To test this hypothesis, capsules are cultured in chondrogenic differentiation medium without TGF-β3. Their biological outcome is compared with capsules encapsulating microparticles without TGF-β3 immobilization and cultured in normal chondrogenic differentiation medium containing soluble TGF-β3. Glycosaminoglycans quantification demosntrates that similar chondrogenesis levels are achieved. Moreover, collagen fibrils resembling the native ...
Conditions: Knee Cartilage Defects; OsteoarthritisIntervention: Biological: Bone marrow derived mesenchymal stem cellsSponsors: Royan Institute; Tehran...
Randau TM, Schildberg FA, Alini M, Wimmer MD, Haddouti el-M, Gravius S, Ito K, Stoddart MJ; The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.; PLoS One, 2013 PubMed Europe PMC Scholia ...
Expresses markers specific to mesenchymal cells derived from neural crest and lateral plate mesoderm. Demonstrated in vitro chondrogenic and osteogenic differentiation Demonstrate in vivo cartilage repair in a rat model.
Expresses markers specific to mesenchymal cells derived from neural crest and lateral plate mesoderm. Demonstrated in vitro chondrogenic and osteogenic differentiation Demonstrate in vivo cartilage repair in a rat model.
Sigma-Aldrich offers abstracts and full-text articles by [Takako Hattori, Francoise Coustry, Shelley Stephens, Heidi Eberspaecher, Masaharu Takigawa, Hideyo Yasuda, Benoit de Crombrugghe].
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 ...
Objectives Chondrocytes, the only cells in the articular cartilage, play a pivotal role in osteoarthritis (OA) because they are responsible for maintenance of the extracellular matrix (ECM). Follistatin-like protein 1 (FSTL1) is a secreted protein found in mesenchymal stem cells (MSCs) and cartilage but whose function is unclear. FSTL1 has been shown to modify cell growth and survival. In this work, we sought to determine whether FSTL1 could regulate chondrogenesis and chondrogenic differentiation of MSCs.. ...
Approach and Results-Here, we show that Wnt/β-catenin signaling inhibits Sox9 nuclear localization and proteoglycan expression in cultured chicken embryo aortic valves. Loss of β-catenin in vivo in mice, using Periostin(Postn)Cre-mediated tissue-restricted loss of β-catenin (Ctnnb1) in valvular interstitial cells, leads to the formation of aberrant chondrogenic nodules and induction of chondrogenic gene expression in adult aortic valves. These nodular cells strongly express nuclear Sox9, and Sox9 downstream chondrogenic extracellular matrix genes, including Aggrecan, Col2a1, and Col10a1. Excessive chondrogenic proteoglycan accumulation and disruption of stratified extracellular matrix maintenance in the aortic valve leaflets are characteristics of myxomatous valve disease. Both in vitro and in vivo data demonstrate that the loss of Wnt/β-catenin signaling leads to increased nuclear expression of Sox9 concomitant with induced expression of chondrogenic extracellular matrix proteins.. ...
Stem cell-based tissue engineering has provided an alternative strategy to treat cartilage lesions, and synovium-derived mesenchymal stem cells (SMSCs) are considered as a promising cell source for cartilage repair. In this study, the SMSCs were isol
Somogyi, C, Matta, C, Foeldvari, Z, Katona, E, Takacs, RA, Juhasz, T, Nanasi, PP, Hegyi, B, Szentandrassy, N and Zakany, R (2012) Embryonic chicken and murine chondrogenic cells express TRPV1 channels that influence cartilage formation In: 22nd International-Union-of-Biochemistry-and-Molecular-Biology (IUBMB) Congress/37th Federation-of-European-Biochemical-Societies (FEBS) Congress, 2012-09-04 - 2012-09-09, Seville, SPAIN. Full text not available from this repository ...
In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared to healthy ...
Disclosed are neocartilage compositions characterized by having multiple layers of cells, said cells being surrounded by a substantially continuous insoluble glycosaminoglycan and collagen-enriched hyaline extracellular matrix, and which neocartilage phospholipids are advantageously enriched in anti-inflammatory n-9 fatty acids, particularly 20:3 n-9 eicosatrienoic or Mead acid. Also disclosed are methods of growing neocartilage in substantially serum-free growth media and methods of producing a conditioned growth media containing compounds effective to enhance neocartilage formation. The neocartilage compositions are useful as implants and as replacement tissue for damaged or defective cartilage and as a model system for studying articular cartilage disease and response to natural and synthetic compounds.
Fibroblast growth factors (FGFs) play an essential role in development and patterning of the vertebrate embryo. Despite extensive literature documenting the diverse roles of FGF signalling during craniofacial development, comparatively little is known about the specific downstream effectors through which FGFs influence gene expression. A previous study in our laboratory reported exogenous FGF elicited differential chondrogenic responses in frontonasal and mandibular mesenchyme (Bobick et al., 2007). Pea3 transcription factors are crucial components of the downstream effector pathway through which FGFs influence gene expression (Raible and Brand, 2001). Therefore, the purpose of my research was to examine whether differences in pea3, erm, and er81 gene expression profiles underlie the distinct responses of the frontonasal and mandibular mesenchyme cells to FGF. The present study demonstrates that FGF2 treatment differentially affects chondrogenesis in micromass cultures of frontonasal and ...
in Developmental Dynamics : An Official Publication of the American Association of Anatomists (1999), 216(3), 233-43. To define genes specifically expressed in cartilage and during chondrogenesis, we compared by differential display-polymerase chain reaction (DD-PCR) the mRNA populations of differentiated sternal ... [more ▼]. To define genes specifically expressed in cartilage and during chondrogenesis, we compared by differential display-polymerase chain reaction (DD-PCR) the mRNA populations of differentiated sternal chondrocytes from chicken embryos with mRNA species modulated in vitro by retinoic acid (RA). Chondrocyte-specific gene expression is downregulated by RA, and PCR-amplified cDNAs from both untreated and RA-modulated cells were differentially displayed. Amplification products only from RNA of untreated chondrocytes were further analyzed, and a cDNA-fragment of the chondromodulin-I (ChM-I) mRNA was isolated. After obtaining full length cDNA clones, we have analyzed the mRNA ...
When DArcy Wentworth Thompsons On Growth and Form was published 100 years ago, it raised the question of how biological forms arise during development and across evolution. In light of the advances in molecular and cellular biology since then, a succinct modern view of the question states: how do genes encode geometry? Our new special issue is packed with articles that use mathematical and physical approaches to gain insights into cell and tissue patterning, morphogenesis and dynamics, and that provide a physical framework to capture these processes operating across scales.. Read the Editorial by guest editors Thomas Lecuit and L. Mahadevan, as they provide a perspective on the influence of DArcy Thompsons work and an overview of the articles in this issue.. ...
Different forms of biomaterials, including microspheres, sponges, hydrogels, and nanofibers, have been broadly used in cartilage regeneration; however, effects of internal structures of the biomaterials on cells and chondrogenesis remain largely unex
Angele, Peter, Müller, Rainer, Schumann, Detlef, Englert, Carsten, Zellner, J., Johnstone, Brian M., Yoo, J.U., Nerlich, Michael und Kujat, R. (2009) Characterization of esterified hyaluronan-gelatin polymer composites suitable for chondrogenic differentiation of mesenchymal stem cells. Journal of Biomedical Materials Research, Part A 91A (2), S. 416-427 ...
Vujovic, S., Henderson, Stephen R., Clements, Mark O. and Flanagan, A.M. (2005) Patterns of gene expression and novel factors involved in cartilage development identified through transcriptional analysis of hMSC chondrogenesis. In: Keystone Symposium 2005: Molecular Regulation of Stem Cells, 10-15 Feb 2005, Banff, Canada. (Submitted ...
Signaling pathway components such as Ihh/Pthrp, TGF?, BMPs, Wnt/?-catenin, FGFs, and Sox-related proteins represent important regulators of cartilage formation...
Complete information for SCRG1 gene (Protein Coding), Stimulator Of Chondrogenesis 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Cytotoxic T-lymphocyte-associated protein 4- (CTLA4-) modified human bone marrow-derived mesenchymal stem cells (hBMMSCs) might be promising seed cells for bone tissue engineering. However, the underlying mechanism is not clear. In the present study, we investigated whether CTLA4-modified hBMMSCs are involved in the migration of allogeneic hBMMSCs (allo-hBMMSCs) by maintaining POSTN secretion. hBMMSCs were isolated from different groups, named hBMMSCs and allo-hBMMSCs. hBMMSCs that were infected with the negative control (NC), empty adenovirus- or recombinant adenovirus-expressing CTLA4, POSTN, or CTLA4 plus the shRNA of POSTN were named NC hBMMSCs, CTLA4-modified hBMMSCs, POSTN-modified hBMMSCs, or CTLA4+shPOSTN-modified hBMMSCs, respectively. They were then cocultured with PBMCs in a 1 : 5 ratio with 2.5 |i|μ|/i|g/mL phytohemagglutinin (PHA). The coculture supernatant was collected to treat allo-hBMMSCs with anti-integrin |i|α|/i|v|i|β|/i|3 IgG, or negative
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 ...
SoxE genes include a group of transcription factors (Sox8, Sox9, and Sox10) that are among key regulators of neural crest cell (NCC) development. The functional redundancy among SoxE paralogs and orthologs suggests that a function of the ancestral SoxE gene was likely in NCC regulation. Here, we investigate the inter-specific functional redundancy of SoxE genes among species that occupy critical phylogenetic positions. Using a heterospecific expression approach, we show that amphioxus and lamprey SoxE genes can induce phenotypic rescue of NCC derivatives when expressed in zebrafish mutant backgrounds. Our results suggest that the amphioxus SoxE gene can drive chondrogenesis, melanogenesis, and neurogenesis when expressed in jellyfish (Sox9a-/-) and colourless (Sox10-/-) mutants. Lamprey SoxE1 can induce cartilage condensations while SoxE2 and SoxE3, the lamprey ortholog of Sox9, have no effect on chondrogenesis. Surprisingly, expression of SoxE2 results in rescue of melanogenesis and ...
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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 ...
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The Global Cartilage Regeneration Market was worth USD 421.5 million in 2016 and is projected to be growing at a CAGR of 14.2%, to touch USD 818.71 million by 2021.
This gene encodes a member of the homeobox transcription factor family. A highly related protein in mouse has been shown to influence cellular processes that control cell adhesion and remodeling of the actin cytoskeleton in myoblast fusion and chondrogenesis. The encoded protein may also play a role in cancer progression ...
Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. Despite progress in orthopaedic surgery, the lack of efficient modalities of treatment for large chondral defects has prompted research on tissue engineering combining chondrogenic cells, scaffold materials and environmental factors. The aim of this review is to focus on the recent advances made in exploiting the potentials of cell therapy for cartilage engineering. These include: 1) defining the best cell candidates between chondrocytes or multipotent progenitor cells, such as multipotent mesenchymal stromal cells (MSC), in terms of readily available sources for isolation, expansion and repair potential; 2) engineering biocompatible and biodegradable natural or artificial matrix scaffolds as cell carriers, chondrogenic factors releasing factories and supports for defect filling, 3) identifying more specific growth factors and the appropriate
The purpose of this study was to develop a fibrin gel system capable of serving as a three dimensional scaffold for the chondrogenesis of rabbit bone marrow mesenchymal stem cells (BM-MSCs) and to examine the effect of two fibrinolytic inhibitors, aprotinin and aminohexanoic acid, on this system. Rabbit BM-MSCs were obtained from the tibias and femurs of New Zealand white rabbits. After chondrogenic potential of BM-MSCs was verified by pellet culture, 2 x 106 cells were pelleted and suspended in fibrinogen (80mg/ml) and then mixed with equal parts of thrombin (5 IU/ml). The specimen were then divided into four groups: aprotinin control (with aprotinin); aprotinin + transforming growth factor (TGF-beta) (with aprotinin and TGF-beta 1); amino control (with aminohexanoic acid); and amino+TGF-beta (with aminohexanoic acid and TGF- beta1). Each of these groups was further divided into three groups depending on the concentration of the inhibitor. Both of the aprotinin groups received 0.0875, 0.175, or 0.35
During appendicular skeletal development, the bi-potential cartilage anlagen gives rise to transient cartilage, which is eventually replaced by bone, and to articular cartilage that caps the ends of individual skeletal elements. While the molecular mechanism that regulates transient cartilage differentiation is relatively well understood, the mechanism of articular cartilage differentiation has only begun to be unraveled. Furthermore, the molecules that coordinate the articular and transient cartilage differentiation processes are poorly understood. Here, we have characterized in chick the regulatory roles of two transcription factors, NFIA and GATA3, in articular cartilage differentiation, maintenance and the coordinated differentiation of articular and transient cartilage. Both NFIA and GATA3 block hypertrophic differentiation. Our results suggest that NFIA is not sufficient but necessary for articular cartilage differentiation. Ectopic activation of GATA3 promotes articular cartilage ...
Damage of cartilage due to traumatic or pathological conditions results in disability and severe pain. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function. Fresh fibrin (FG) and platelet-rich fibrin (PR-FG) glues produced by the CryoSeal (R) FS System, in combination with human bone marrow-derived mesenchymal stem cells (BM-hMSCs), were evaluated in this study. We additionally tested the incorporation of heparin-based delivery system (HBDS) into these scaffolds to immobilize endogenous growth factors as well as exogenous transforming growth factor-beta(2). Strongly, CD90+ and CD105+ hMSCs were encapsulated into FG and PR-FG with and without HBDS. Encapsulation of hMSCs in PR-FG led to increased expression of collagen II gene at 2.5 weeks; however, no difference was observed between FG and PR-FG at 5 weeks. The incorporation of HBDS prevented the enhancement ...
Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.
Applications of bone marrow-derived mesenchymal stem cells (BM-MSCs) have been documented for diseases occur in the sports system, the central nervous system, the cardiov..
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 ...
The first step in growing new cartilage is initiating chondrogenesis, or convincing the mesenchymal stem cells to differentiate into chondrocytes, which in turn generate the spongy matrix of collagen and sugars that cushions joints. One challenge in prompting this differentiation is that, despite the low density of adult chondrocytes in tissues, the actual formation of cartilage begins with cells in close proximity. "In typical hydrogels used in cartilage tissue engineering," Burdick said, "were spacing cells apart, so theyre losing that initial signal and interaction. Thats when we started thinking about cadherins, which are molecules that these cells use to interact with each other, particularly at the point they first become chondrocytes.". To simulate that environment, the researchers used a peptide sequence that mimics these cadherin interactions, which they bound to the hydrogels used to encapsulate the mesenchymal stem cells.. "While the direct link between cadherins and chondrogenesis ...
Everything you always wanted to know about cartilaginous tissue, but were affraid to ask - what is it built of, what types of cartilaginous tissue can we single out and what are characteristic features of each type. Types of cartilaginous tissue - hyaline tissue, elastic tissue, fibrous tissue.
Chondroblasts, or perichondrial cells, is the name given to mesenchymal progenitor cells in situ which, from endochondral ossification, will form chondrocytes in the growing cartilage matrix. Another name for them is subchondral cortico-spongious progenitors. They have euchromatic nuclei and stain by basic dyes. These cells are extremely important in Chondrogenesis due to their role in forming both the Chondrocytes and cartilage matrix which will eventually form cartilage. Use of the term is technically inaccurate since mesenchymal progenitors can also technically differentiate into osteoblasts or fat. Chondroblasts are called Chondrocytes when they embed themselves in the cartilage matrix, consisting of proteoglycan and collagen fibers, until they lie in the matrix lacunae. Once they embed themselves into the cartilage matrix, they grow the cartilage matrix by growing more cartilage extracellular matrix rather than by dividing further.[citation needed] As suggested in the name, mesenchymal ...
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Bone marrow stromal cells from embryonic, neo-natal and adult chickens were grown in vitro over a 21-day period. Marrow stromal cells from embryonic and neonatal chicks produced clonally derived chondrocytic colonies. The cells within the colonies were surrounded by a refractile, Alcian-blue-positive matrix and their cartilagenous nature was shown biochemically and immunocytochemically by the synthesis of collagen types II and X. The ability of chick bone marrow cells to form chondrocytic colonies decreased during development and was lost by adulthood. In addition to chondrocytic colonies, fat cells and fibroblasts were also observed in the cultures. Our data demonstrate that chick bone marrow stroma contains cells that are capable of differentiating along different pathways within the same culture, providing further evidence for the presence in bone marrow of a stromal stem cell.. ...
TY - JOUR. T1 - Expression of runtB is modulated during chondrocyte differentiation. AU - Castagnola, Patrizio. AU - Gennari, Massimo. AU - Gaggero, Alessia. AU - Rossi, Fabio. AU - Daga, Antonio. AU - Corsetti, Maria Teresa. AU - Calabi, Franco. AU - Cancedda, Ranieri. PY - 1996/3/15. Y1 - 1996/3/15. N2 - The runt locus in Drosophila encodes a nuclear protein involved in embryo segmentation, sex determination/X dosage compensation, and neurogenesis. runt homologues have been identified in higher vertebrates. The encoded proteins share a domain of 128 amino acids called the runt domain. It has been reported that this domain mediates DNA binding and heterodimerization. Here, we analyze runtB expression during chondrocyte differentiation in vitro and in vivo. We have first isolated, from a chondrocyte library, a cDNA clone coding for a runtB chicken homologue and containing a complete open reading frame. The predicted protein product is 84% identical to the mouse PEBP2αB2 isoform. By RT-PCR ...
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A group of researchers at Osaka University developed a synthetic tissue using synovium-derived mesenchymal stem cells (MSCs) for treating damaged cartilage, which had previously been incurable and had no effective therapies.
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If you want to explore the biological basis for short stature, then an excellent review (YH Jee, J Bacon. J Pediatr 2016; 173: 32-7) is worthwhile. The article begins by explaining the reasons why linear growth is rapid in infancy, slows in childhood and accelerates in adolescence through a process of growth plate chondrogenesis. In addition,…
Zamani, S. and Dehghani, Leila. and Drummen, G. and esfandiari, Ebrahim. and Abutorabi, Roshanak. and Rabbani, Hossein. and Tahani, Soheil. and Hashemi beni, Batool. (2016) Comparison of cartilage specific markers in articular and differentiated chondrocytes in pellet system. Biointerface Research in Applied Chemistry, 6 (6). Zamani, Saeed. and Hashemibeni, Batool. and esfandiari, Ebrahim. and Kabiri, Azadeh. and Rabbani, Hossein. and Abutorabi, Roshanak. (2014) Assessment of TGF-β3 on production of aggrecan by human articular chondrocytes in pellet culture system. Advanced Biomedical Research. ...
J:122952 Hung IH, Yu K, Lavine KJ, Ornitz DM, FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod. Dev Biol. 2007 Jul 15;307(2):300-13 ...
Reactivity: Cow (Bovine), Dog (Canine) Host: Rabbit Clone: Polyclonal 1 image 1 PubMed reference | Order NCF4 antibody (ABIN2782428).
TY - JOUR. T1 - C-type natriuretic peptide/guanylate cyclase B system in ATDC5 cells, a chondrogenic cell line. AU - Suda, Michio. AU - Tanaka, Kiyoshi. AU - Yasoda, Akihiro. AU - Komatsu, Yasato. AU - Chusho, Hideki. AU - Miura, Masako. AU - Tamura, Naohisa. AU - Ogawa, Yoshihiro. AU - Nakao, Kazuwa. PY - 2002/12/1. Y1 - 2002/12/1. N2 - Natriuretic peptides constitute a family of three structurally related peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Particulate guanylate cyclases, GC-A, and GC-B, are the receptors for these peptides to mediate their action. ANP and BNP possess high affinities for GC-A, and CNP is the preferred ligand for GC-B. In this article, we report our study of the expression and possible role(s) of natriuretic peptides in ATDC5 cells, which represent a chondrogenic cell line. ATDC5 cells produced cyclic guanosine monophosphate (cGMP) in response to natriuretic peptides. CNP was far more potent than ANP ...
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 ...
BACKGROUND: Articular cartilage repair in the knee is aimed at young patients with area(s) of cartilage loss and no deformity of the knee. These patients arent indicated for a knee replacement. Articular cartilage repair leads to improvement of symptoms of pain, locking and function. Traditionally, articular cartilage repair has always involved exposing the entire knee joint with an arthrotomy. This, though effective, would lead to a large scar, longer hospital stay, longer rehabilitation and its associated complications. Also, the use of Bone Marrow Aspirate Cells (BMAC) for the purpose of cartilage repair has long been debated with both sides having valid arguments and good surgical results.. RATIONALE: Both procedures in this study are performed in one stage, arthroscopically and as day case procedures, which offers minimal scarring and quicker recovery. This automatically confers a significant advantage over the traditional surgical techniques.. To correct the articular cartilage defect, ...
Production, means the output of Cartilage Repair/ Cartilage Regeneration Revenue, means the sales value of Cartilage Repair/ Cartilage Regeneration This report studies Cartilage Repair/ Cartilage Regeneration in Global market, especially in North America, Europe, China, Japan, Southeast Asia and India, focuses on top manufacturers in global market, with production, price, revenue and market share
The global Human Mesenchymal Stem Cells (hMSC) market is exhaustively researched and analyzed in the report to help market players to improve their business tactics and ensure long-term success. The authors of the report have used easy-to-understand language and uncomplicated statistical images but provided thorough information and detailed data on the global Human Mesenchymal Stem Cells (hMSC) market. The report equips players with useful information and suggests result-oriented ideas to gain a competitive edge in the global Human Mesenchymal Stem Cells (hMSC) market. It shows how different players are competing in the global Human Mesenchymal Stem Cells (hMSC) market and discusses about strategies they are using to distinguish themselves from other participants.. Get the Sample of this [email protected]://www.qyresearch.com/sample-form/form/904648/global-human-mesenchymal-stem-cells-hmsc-market. The researchers have provided quantitative and qualitative analysis along with absolute dollar ...
Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Here, we describe that serum- and glucocorticoid-inducible kinase 1 (SGK1) was upregulated in VSMCs under calcifying conditions. In primary human aortic VSMCs, overexpression of constitutively active SGK1S422D, but not inactive SGK1K127N, upregulated osteo-/chondrogenic marker expression and activity, effects pointing to increased osteo-/chondrogenic transdifferentiation. SGK1S422D induced nuclear translocation and increased transcriptional activity of NF-κB. Silencing or pharmacological inhibition of IKK abrogated the osteoinductive effects of SGK1S422D. Genetic deficiency, silencing, and pharmacological inhibition of SGK1 dissipated phosphate-induced calcification and osteo-/chondrogenic transdifferentiation of VSMCs. Aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation in ...
Inactivation of Gli3, a key component of Hedgehog signaling in vertebrates, results in formation of additional digits (polydactyly) during limb bud development. The analysis of mouse embryos constitutively lacking Gli3 has revealed the essential GLI3 functions in specifying the anteroposterior (AP) limb axis and digit identities. We conditionally inactivated Gli3 during mouse hand plate development, which uncoupled the resulting preaxial polydactyly from known GLI3 functions in establishing AP and digit identities. Our analysis revealed that GLI3 directly restricts the expression of regulators of the G(1)-S cell-cycle transition such as Cdk6 and constrains S phase entry of digit progenitors in the anterior hand plate. Furthermore, GLI3 promotes the exit of proliferating progenitors toward BMP-dependent chondrogenic differentiation by spatiotemporally restricting and terminating the expression of the BMP antagonist Gremlin1. Thus, Gli3 is a negative regulator of the proliferative expansion of digit
...A research team led by Professor Noriyuki Tsumaki of the Center for iP...Articular cartilage which is made up of chondrocytes and extracellula...Normal articular cartilage consists of hyaline cartilage but when thi...One conceivable method of producing cartilage would be to induce it fr...,Direct,induction,of,chondrogenic,cells,from,human,dermal,fibroblast,culture,by,defined,factors,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology
The development of biologically and mechanically competent hydrogels is a prerequisite in cartilage engineering. We recently demonstrated that a marine exopolysaccharide, GY785, stimulates the in vitro chondrogenesis of adipose stromal cells. In the present study, we thus hypothesized that enriching our silated hydroxypropyl methylcellulose hydrogel (Si-HPMC) with GY785 might offer new prospects in the development of scaffolds for cartilage regeneration. The interaction properties of GY785 with growth factors was tested by surface plasmon resonance (SPR). The biocompatibility of Si-HPMC/GY785 towards rabbit articular chondrocytes (RACs) and its ability to maintain and recover a chondrocytic phenotype were then evaluated in vitro by MTS assay, cell counting ...
A redifferentiated dermal fibroblast cell that exhibits at least one characteristic of a chondrocyte. A proteoglycan is used to induce re-differentiation of the cell. In some embodiments, the cell expresses of at least one cartilage proteoglycan marker. The proteoglycan may comprise aggrecan and the cell may differentiate from the fibroblast along the chondrogenic lineage. A method of inducing chondrogenesis in a fibroblast cell comprises culturing the fibroblast cell on a surface containing at least one cartilage-derived proteoglycan other than perlecan. A three-dimensional scaffold may be coated with the proteoglycan and seeded with fibroblast cells. The fibroblast cells may be contacted with at least one chondrogenic growth factor or cytokine prior to said culturing.
Differentiation of stem cells to chondrocytes in vitro usually results in a heterogeneous phenotype. This is evident in the often detected over expression of type X collagen which, in hyaline cartilage structure is not characteristic of the mid-zone but of the deep-zone ossifying tissue. Methods to better match cartilage developed in vitro to characteristic in vivo features are therefore highly desirable in regenerative medicine. This study compares phenotype characteristics between pericytes, obtained from human adipose tissue, differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the more widely used chemical induced method for chondrogenesis. Significantly higher levels of type II collagen were noted when pericytes undergo chondrogenesis in the hydrogel in the absence of induction media. There is also a balanced expression of collagen relative to aggrecan production, a feature which was biased toward collagen production when cells were cultured with induction media. ...
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National Documentation Centre (EKT). National Archive of PhD Theses.PhD thesis.2014 . Creators: Makris, Eleftherios, Μακρής, Ελευθέριος.Ο αρθρικός και ο ινώδης χόνδρος έχουν περιορισμένη ικανότητα αναγέννησης μετά από τραυματικές κακώσεις και παθήσεις των αρθρώσεων. Δεδομένου του κριτικού ρόλου των ιστών αυτών στην προστασία των αρθρικών οστικών δομών και στην εξασφάλιση σταθερών λειτουργικών αρθρώσεων, η ανάπτυξη μεθόδων που προάγουν την αναγέννηση ή / και την επιδιορθώση των ιστών αυτών ειναι εξαιρετικά σημαντική. Η επιστήμη της ανάπτυξης μηχανικών ιστών παρέχει σήμερα εξαιρετικές προοπτικές
p,Osteoarthritis (OA) is one of the leading causes of disability in the United States, afflicting over 27 million Americans and imposing an economic burden of more than $128 billion each year (1, 2). OA is characterized by progressive degeneration of articular cartilage together with sub-chondral bone remodeling and synovial joint inflammation. Currently, OA treatments are limited, and inadequate to restore the joint to its full functionality. ,/p,,p,Over the years, progresses have been made to create biologic cartilage substitutes. However, the repair of degenerated cartilage remains challenging due to its complex architecture and limited capability to integrate with surrounding tissues. Hence, there exists a need to create not only functional chondral constructs, but functional osteochondral constructs, which could potentially enhance affixing properties of cartilage implants utilizing the underlying bone. Furthermore, the molecular mechanisms driving chondrogenesis are still not fully ...
Functional tissue engineering of cartilage involves the use of bioreactors designed to provide a controlled in vitro environment that embodies some of the biochemical and physical signals known to regulate chondrogenesis. Hydrodynamic conditions can
This webinar explores the applied anatomy, aetiology and biomechanics of the infrapatellar fat pad. The webinar is underpinned by evidence and clinical reasoning, and Claire draws on her extensive experience of assessing and treating this patient group to present the topic with maximum clinical relevance.. On receipt of payment a link will be sent for the webinar.. ...
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Looking for online definition of cartilaginous tissue in the Medical Dictionary? cartilaginous tissue explanation free. What is cartilaginous tissue? Meaning of cartilaginous tissue medical term. What does cartilaginous tissue mean?
Newton PT, Li L, Zhou B, Schweingruber C, Hovorakova M, Xie M, Sun X, Sandhow L, Artemov AV, Ivashkin E, Suter S, Dyachuk V, El Shahawy M, Gritli-Linde A, Bouderlique T, Petersen J, Mollbrink A, Lundeberg J, Enikolopov G, Qian H, Fried K, Kasper M, Hedlund E, Adameyko I, Sävendahl L, Chagin AS Nature 567 (7747) 234-238 [2019-03-00; online 2019-02-27] Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification 1. However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth1,2, but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of ...
... is the degree of maturation of a child's bones. As a person grows from fetal life through childhood, puberty, and finishes growth as a young adult, the bones of the skeleton change in size and shape. These changes can be seen by x-ray. The "bone age" of a child is the average age at which children reach this stage of bone maturation. A child's current height and bone age can be used to predict adult height. For most people, their bone age is the same as their biological age but for some individuals, their bone age is a couple years older or younger. Those with advanced bone ages typically hit a growth spurt early on but stop growing early sooner while those with delayed bone ages hit their growth spurt later than normal. Kids who are below average height do not necessarily have a delayed bone age; in fact their bone age could actually be advanced which if left untreated, will stunt their growth. At birth, only the metaphyses of the "long bones" are present. The long bones are those that ...
Schipani E (2006). "Hypoxia and HIF-1 alpha in chondrogenesis". Semin. Cell Dev. Biol. 16 (4-5): 539-46. doi:10.1016/j.semcdb. ...
Schipani E (2006). "Hypoxia and HIF-1 alpha in chondrogenesis". Seminars in Cell & Developmental Biology. 16 (4-5): 539-46. doi ...
Liu C (2006). "Transcriptional mechanism of COMP gene expression and chondrogenesis". Journal of Musculoskeletal & Neuronal ...
Juhász T, Helgadottir SL, Tamás A, Reglődi D, Zákány R (April 2015). "PACAP and VIP signaling in chondrogenesis and ...
The encoded protein may play a role in chondrogenesis. A pseudogene of this gene is located on chromosome 8. Multiple ... Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene". The EMBO Journal. 17 (19 ...
Additional studies emphasized the role of Sulfs in chondrogenesis. The role of QSulf1 was determined in quail cartilage ... 2008). Also, the zone of proliferating chondrocytes was reduced by 90%, indicating defects in chondrogenesis. The important ... Because Sulfs were important in normal chondrogenesis, they were investigated in cartilage diseases. Expression patterns of ... indicating QSulf1 is needed for early chondrogenesis. QSulf1 displayed perichondrial staining during early development but was ...
TGF-β will act as a stimulator of chondrogenesis, and an inhibitor of osteoblastic differentiation, by blocking the Runx2 ... "The role of TGFβs and Sox9 during limb chondrogenesis". Current Opinion in Cell Biology. 18 (6): 723-729. doi:10.1016/j.ceb. ... as the sites for osteogenesis and chondrogenesis are now known. Osteochondroprogenitor can be found between MSCs and the ... suggesting that they are important in chondrogenesis. Osteoblasts are cells that group together to form units, called osteons, ...
Rodrigo JJ, Steadman JR, Syftestad G, Benton H, Silliman J (1995). "Effects of human knee synovial fluid on chondrogenesis in ... supporting both osteogenesis and chondrogenesis. With disruption of the epiphyseal plate vessels, varying degrees and depth of ...
"The expression and function of microRNAs in chondrogenesis and osteoarthritis". Arthritis & Rheumatism. 64 (6): 1909-1919. doi: ...
"MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression". Osteoarthritis and Cartilage. 20 (6): 593 ...
"Regulation of growth plate chondrogenesis by bone morphogenetic protein-2". Endocrinology. 142 (1): 430-436. doi:10.1210/en. ...
"Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development". Development. 130 (12 ...
Gomes RR, Farach-Carson MC, Carson DD (2004). "Perlecan functions in chondrogenesis: insights from in vitro and in vivo models ...
... signals through fibroblast growth factor receptor FGFR3 to promote chondrogenesis and has been shown to cause thickening ... "Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis". ... 18 Signals through FGF Receptor 3 to Promote Chondrogenesis". Journal of Biological Chemistry. 280 (21): 20509-20515. doi: ...
"Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo". Proc. Natl. Acad. Sci. U.S.A. 102 ( ...
18 Signals through FGF Receptor 3 to Promote Chondrogenesis". Journal of Biological Chemistry. 280 (21): 20509-20515. doi: ...
Gamer LW, Cox KA, Small C, Rosen V (Jan 2001). "Gdf11 is a negative regulator of chondrogenesis and myogenesis in the ... and is a negative regulator of chondrogenesis. Due to the similarities between myostatin and GDF11, the actions of GDF11 are ...
"An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis". Nature ...
Csaki C, Matis U, Mobasheri A, Ye H, Shakibaei M (December 2007). "Chondrogenesis, osteogenesis and adipogenesis of canine ...
"Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells". Growth ...
"Chondrogenesis in a cell-polymer-bioreactor system," Experimental Cell Research 240(1), pp. 58-65, 1998. "Professor Gordana ...
Regulates Chondrogenesis via Direct Targeting to Smad1". Journal of Biological Chemistry. 284 (17): 11326-35. doi:10.1074/jbc. ... because it was reported to be specifically expressed in the skeletal system and was shown to inhibit chondrogenesis by down- ...
This technique is known as AMIC (Autologous Matrix-Induced Chondrogenesis) and was first published in 2003. A 2011 study ... the microdrilling surgery creates a blood clot scaffold on which injected PBPC's can be recruited and enhance chondrogenesis at ...
"Spatial and temporal distribution of lamprin mRNA during chondrogenesis of trabecular cartilage in the sea lamprey". Anat ...
... during chondrogenesis. Noggin, a developmental protein, inhibits chondrogenesis by preventing condensation and differentiation ... Chondrogenesis is the process by which cartilage is developed. In embryogenesis, the skeletal system is derived from the ... L-Sox5 is also thought to be involved primarily in embryonic chondrogenesis, while Sox6 is thought to be involved in post-natal ... Chondrification (also known as chondrogenesis) is the process by which cartilage is formed from condensed mesenchyme tissue, ...
Chon`dro*gene*sis (?), n. [Gr. cartilage + genesis.] Physiology|Physiol. The development of cartilage. © Webst...
Autologous matrix-induced chondrogenesis (AMIC) is a treatment for articular cartilage damage. There is tentative short to ... Autologous Matrix Induced Chondrogenesis (AMIC) surgery is a single step procedure. After arthroscopic evaluation of the ... Shaikh, N; Seah, MKT; Khan, WS (18 July 2017). "Systematic review on the use of autologous matrix-induced chondrogenesis for ...
Impaired chondrogenesis and ECM expression in mutants. (A-C) Alcian blue staining of E14.5 (A), E16.5 (B), and postnatal day 0 ... Bmpr1b -/- mice are viable, and defects in chondrogenesis are primarily restricted to distal phalanges (9, 10). Bmpr1aCKO mice ... Because loss of neither Bmpr1a nor Bmpr1b led to major alterations in chondrogenesis, Bmpr1aCKO; Bmpr1b -/- embryos were ... BMPR1A and BMPR1B are functionally redundant during chondrogenesis. (A) Gross appearance of E14.5 WT and Bmpr1aCKO; Bmpr1b -/- ...
H. J. Kwon, "TGF-β but not BMP signaling induces prechondrogenic condensation through ATP oscillations during chondrogenesis," ... We recently found that ATP oscillations play a key role in prechondrogenic condensation during chondrogenesis [2-4]. It was ... In this study, insulin which stimulates chondrogenesis of ATDC5 cells [16] was used in induction of ATP oscillations during ... Metabolomic Analysis of Differential Changes in Metabolites during ATP Oscillations in Chondrogenesis. Hyuck Joon Kwon1 and ...
MSCs undergoing chondrogenesis are preferentially responsive to an electromagnetic efficacy window defined by field amplitude, ... This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on ... PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. The demonstrated efficacy of our optimized PEMF ... have been shown to recruit calcium-signaling cascades common to chondrogenesis. Here we document the effects of specified PEMF ...
Chondrogenesis in a cell-polymer-bioreactor system.. *Lisa E. Freed, Anthony P Hollander, Ivan Martin, John R. Barry, Robert ... Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development.. *Ung-il Chung, Ernestina Schipani, ... Chondrogenesis. Known as: cartilage formation, cartilage organ development, cartilage biogenesis (More). The process whose ... Chondrogenesis was studied under controlled in vitro conditions using a cell-polymer-bioreactor system. Bovine calf articular… ...
Therefore, the aim of this study was to analyse how NE influences the chondrogenesis of synovial adipose tissue-derived stem ... A) Immunohistochemical analysis of β2-AR and α2a-AR during sASC chondrogenesis on days 1, 7, 14, and 21 of differentiation ( ... Effect of NE on sASC chondrogenesis. (A) Macroscopic, and histologic (sGAG) analysis as well as immunohistochemical type II ... Effect of specific AR antagonists on NE effects during sASC chondrogenesis. (A) Macroscopic, histologic (sGAG) analysis and ...
Shakibaei M. (1998) Inhibition of chondrogenesis by integrin antibody in vitro. Exp Cell Res 240:95-106PubMedCrossRefGoogle ... Mesenchymal stem cells Chondrogenesis Adipogenesis Osteogenesis Ultrastructure The research was conducted in part for the ... Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal ... Chondrogenesis, osteogenesis and adipogenesis of canine mesenchymal stem cells: a biochemical, morphological and ...
Fgfr1 Neural crest cell Frontal bone Chondrogenesis Osteogenesis This is a preview of subscription content, log in to check ... In summary, our results indicate that loss of Fgfr1 in neural crest cells leads to heterotopic chondrogenesis and osteogenesis. ... Our results show that specific knockout of Fgfr1 in neural crest cells induced heterotopic chondrogenesis and osteogenesis at ... Fgfr1 conditional-knockout in neural crest cells induces heterotopic chondrogenesis and osteogenesis in mouse frontal bones. ...
... ter and accelerated chondrogenesis than controls. This cell engineered construct has potential use in one-step cartilage repair ... This study evaluated chondrogenesis within a nanofiber polymeric scaffold seeded with isolated untreated chondrocytes, isolated ... This study evaluated chondrogenesis within a nanofiber polymeric scaffold seeded with isolated untreated chondrocytes, isolated ... Wilke, M.M., Nydam, D.V. and Nixon, A.J. (2007) Enhanced early chondrogenesis in articular defects following arthroscopic ...
The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ... The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ... that mutant R206H ACVR1 activated BMP signaling in the absence of BMP ligand and mediated BMP-independent chondrogenesis that ... is an activating mutation that induces BMP signaling in a BMP-independent and BMP-responsive manner to promote chondrogenesis, ...
Lentiviral vector expression of Klf4 enhances chondrogenesis and reduces hypertrophy in equine chondrocytes.. [Saliya ...
... its effects on chondrogenesis. In this model, Dlk1/FA1 functions as a negative regulator of chondrogenesis whose expression is ... suggesting regulation of Dlk1/FA1 by TGF-β1 signaling in chondrogenesis. TGF-β1-induced Smad phosphorylation and chondrogenesis ... In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 1998; 238: 265-272.. *CrossRef , ... Smad3 induces chondrogenesis through the activation of SOX9 via CREB-binding protein/p300 recruitment. J Biol Chem 2005; 280: ...
Author Summary A fundamental problem studied by skeletal biologists is the development of regenerative therapies to replace cartilage tissues impacted by injury or disease, which for individuals affected by osteoarthritis represents nearly half of all of all adults over the age of sixty five. To date, no therapies exist to promote sustained cartilage regeneration, as we have not been able to recapitulate the programming events necessary to instruct cells to form articular cartilage without these cells continuing to differentiate into bone. Our analysis of the early programming events occurring during cartilage formation led to the identification of LncRNA-HIT a long noncoding RNA that is essential for the differentiation of the embryonic limb mesenchyme into cartilage. A genome wide analysis of LncRNA-HITs distribution in the mesenchyme revealed strong association between LncRNA-HIT and numerous genes whose products facilitate cartilage formation. In the absence of LncRNA-HIT, the expression of these
Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5.. [Takako ... Sox9 is a transcription factor of the SRY family required for several steps of chondrogenesis. It activates the expression of ... Consistent with a role of Tip60 in chondrogenesis, addition of Tip60 siRNA to limb-bud micromass cultures delayed chondrocyte ...
Chondrogenesis: The ASC culture was performed from cell "Micromass" starting with a high concentration of cells in a minimal ... Human Suprapatellar Fat Pad-Derived Mesenchymal Stem Cells Induce Chondrogenesis and Cartilage Repair in a Model of Severe ... In Vitro Osteogenesis and Chondrogenesis Are Favored in Suprapatellar ASC. To further assess the stem cell characteristics from ... Alizarin red for osteogenesis and Alcian blue for chondrogenesis, versus infrapatellar. In addition, immunodetection of ...
Genetic deletion of Cyp26b1 negatively impacts limb skeletogenesis by inhibiting chondrogenesis. Helen J. Dranse, Arthur V. ... Genetic deletion of Cyp26b1 negatively impacts limb skeletogenesis by inhibiting chondrogenesis. Helen J. Dranse, Arthur V. ... Genetic deletion of Cyp26b1 negatively impacts limb skeletogenesis by inhibiting chondrogenesis. Helen J. Dranse, Arthur V. ... Genetic deletion of Cyp26b1 negatively impacts limb skeletogenesis by inhibiting chondrogenesis Message Subject (Your Name) has ...
Dual roles of Wnt signaling during chondrogenesis in the chicken limb Message Subject (Your Name) has sent you a message from ... 1997) Inhibition of chondrogenesis by Wnt gene expression in vivo and in vitro. Dev. Biol 185, 104-118. ... 1995) Changes in the expression of fibroblast growth factor receptors mark distinct stages of chondrogenesis in vitro and ... Misexpression of a stabilized form of beta-catenin also results in accelerated chondrogenesis, suggesting that a beta-catenin/ ...
Bone marrow stromal cells from embryonic, neo-natal and adult chickens were grown in vitro over a 21-day period. Marrow stromal cells from embryonic and neonatal chicks produced clonally derived chondrocytic colonies. The cells within the colonies were surrounded by a refractile, Alcian-blue-positive matrix and their cartilagenous nature was shown biochemically and immunocytochemically by the synthesis of collagen types II and X. The ability of chick bone marrow cells to form chondrocytic colonies decreased during development and was lost by adulthood. In addition to chondrocytic colonies, fat cells and fibroblasts were also observed in the cultures. Our data demonstrate that chick bone marrow stroma contains cells that are capable of differentiating along different pathways within the same culture, providing further evidence for the presence in bone marrow of a stromal stem cell.. ...
In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal ... Although chondrogenesis is similar in the overall endochondral skeleton (i.e., every skeletal element except some parts of the ... Yoon, B.S.; Lyons, K.M. Multiple functions of BMPs in chondrogenesis. J. Cell Biochem 2004, 93, 93-103. [Google Scholar] ... Hatakeyama, Y.; Tuan, R.S.; Shum, L. Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis. J. Cell Biochem ...
One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC. Drugs that promote chondrogenesis ... Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis. ... a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis. ...
Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM ... Variations in Chondrogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells in Fibrin/Alginate Blended Hydrogels, Acta ... Variations In Chondrogenesis Of Human Bone Marrow-Derived Mesenchymal Stem Cells in Fibrin/Alginate Blended Hydrogels ... Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM ...
Stem cell Chondrogenesis Adipogenesis, Lineage differentiation This is a preview of subscription content, log in to check ... Li J, Zhao Z, Liu J, Huang N, Long D, Wang J, Li X, Liu Y (2010) MEK/ERK and p38 MAPK regulate chondrogenesis of rat bone ... Im GI, Quan Z (2010) The effects of Wnt inhibitors on the chondrogenesis of human mesenchymal stem cells. Tissue Eng Part A 16( ... Shao HJ, Ho CC, Lee YT, Chen CS, Wang JH, Young TH (2012) Chondrogenesis of human bone marrow mesenchymal cells by transforming ...
Home » Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold ... In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 ... Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the ... Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold. ...
  • To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of mesenchymal stromal cells derived from FOP-iPSCs (FOP-iMSCs). (jci.org)
  • Gene expression profile of multipotent mesenchymal stromal cells: Identification of pathways common to TGFbeta3/BMP2-induced chondrogenesis. (heightquest.com)
  • Furthermore, whereas constitutively active forms of either BMPR1A or BMPR1B promote chondrogenesis, only the overexpression of dominant negative (DN)-BMPR1B, and not DN-BMPR1A or DN-ActR1, blocks these events, suggesting that BMPR1B is the major transducer of BMP signals in limb condensations ( 5 - 8 ). (pnas.org)
  • These data support the conclusion that the mutant R206H ACVR1 receptor in FOP patients is an activating mutation that induces BMP signaling in a BMP-independent and BMP-responsive manner to promote chondrogenesis, consistent with the ectopic endochondral bone formation in these patients. (jci.org)
  • Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis. (nih.gov)
  • Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone, or combined with other techniques to greatly assist the therapeutic outcomes. (nih.gov)
  • Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis. (nih.gov)
  • FGF18 signals through fibroblast growth factor receptor FGFR3 to promote chondrogenesis and has been shown to cause thickening of cartilage in a murine model of osteoarthritis, and the recombinant version of it (sprifermin) will soon enter trials as a potential treatment for osteoarthritis. (wikipedia.org)
  • Understanding the molecular basis of Sox9 expression in chondrogenesis will identify potential pharmacological therapeutic targets, which may have clinical implications for the treatment of skeletal dysplasias and degenerative cartilage diseases such as osteoarthritis. (grantome.com)
  • BACKGROUND: Epigenetic changes (i.e., chromatin modifications) occur during chondrogenesis and in osteoarthritis (OA). (ox.ac.uk)
  • Conversely, ERK1/2 is usually a positive regulator of chondrogenesis in BMP-2 induced C3H10T1/2 cultures . (cylch.org)
  • GDF11 is also a negative regulator of neurogenesis, the production of islet progenitor cells, the regulation of kidney organogenesis, pancreatic development, the rostro-caudal patterning in the development of spinal cords, and is a negative regulator of chondrogenesis. (wikipedia.org)
  • Among them, miR-199a* is of particular interest, because it was reported to be specifically expressed in the skeletal system and was shown to inhibit chondrogenesis by down-regulation of Smad1, a major regulator of bone and cartilage formation and development. (wikipedia.org)
  • Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. (morganlewis.com)
  • Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft. (ebscohost.com)
  • NC Cheng, BT Estes, TH Young, and F Guilak, "Genipin-crosslinked cartilage-derived matrix as a scaffold for human adipose-derived stem cell chondrogenesis ," Tissue Eng Part A, vol. (freethesaurus.com)
  • Khay Yong Saw and his team propose that the microdrilling surgery creates a blood clot scaffold on which injected PBPC's can be recruited and enhance chondrogenesis at the site of the contained lesion. (wikipedia.org)
  • Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. (semanticscholar.org)
  • Therefore, the aim of this study was to analyse how NE influences the chondrogenesis of synovial adipose tissue-derived stem cells (sASCs). (nih.gov)
  • Using RNA blot analysis of developmentally staged avian limb buds, we demonstrate that transcripts of several cartilage marker genes appear in limb tissue prior to overt chondrogenesis. (biologists.org)
  • Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGFbeta1 in platelet-rich plasma. (freethesaurus.com)
  • Prior work has established that transient Shh signals from the notochord and floor plate confer a competence in somitic tissue for subsequent BMP signals to induce chondrogenesis. (semanticscholar.org)
  • Chondrogenesis is the process by which cartilage is formed from condensed mesenchyme tissue. (biomedcentral.com)
  • Bioreactor can provide the mechanical and chemical stimuli along with the required cytokines (Cytl1, TNF-α, ROS), mitogen (IL-18, FGF-2, Protein Kinase C-Erk-1/2 and p38), and growth factors (IGF-1, TGF-β, parathyroid hormone-related peptide, BMP-2) to modulate chondrogenesis and grow threedimensional (3-D) tissue. (eurekaselect.com)
  • C. Mahapatra, K. Pramanik and M.K. Gupta, "Factors Modulating Chondrogenesis and Mechano-Inductive Systems for Cartilage Tissue Engineering from Mesenchymal Stem Cells: A Review", Current Tissue Engineering (Discontinued) (2013) 2: 41. (eurekaselect.com)
  • We investigated the effect of H3K27me3 demethylase inhibition on chondrogenesis and assessed its utility in cartilage tissue engineering and in understanding cartilage destruction in OA. (ox.ac.uk)
  • CONCLUSIONS: Overall, we show that H3K27me3 demethylases modulate chondrogenesis and that enhancing this activity may improve production of tissue-engineered cartilage. (ox.ac.uk)
  • The precocious appearance of several cartilage marker gene transcripts prior to chondrogenesis suggests that multiple levels of gene regulation including alternative promoter use, alternative RNA splicing, alternative polyadenylation, and other post-transcriptional as well as translational mechanisms are active prior to, and during avian limb chondrogenesis. (biologists.org)
  • In developing mouse limbs, Yap was nuclear in the perichondrium while mostly phosphorylated and cytosolic in cells of the cartilage anlage, suggesting downregulation of Yap co-transcriptional activity during physiological chondrogenesis in vivo . (biomedcentral.com)
  • In summary, our study demonstrates that BMPR1A and BMPR1B are functionally redundant during early chondrogenesis and that BMP signaling is required for chondrocyte proliferation, survival, and differentiation in vivo . (pnas.org)
  • Consistent with a role of Tip60 in chondrogenesis, addition of Tip60 siRNA to limb-bud micromass cultures delayed chondrocyte differention. (sigmaaldrich.com)
  • Taken together, these findings indicate that ATF6a favorably controls chondrogenesis and bone formation (1) by acting as a co-factor of Runx2 and enhancing Runx2-incited hypertrophic chondrocyte differentiation, and (2) by affecting IHH and PTHrP signaling. (biologists.org)
  • The genes belonging to class 1 correspond to genes barely but continuously expressed during chondrogenesis and involved in chondrocyte proliferation and cell cycle regulation. (heightquest.com)
  • Chondrogenesis was assessed by real-time RT-PCR for chondrocyte-associated genes, by immunohistochemistry and by ELISA for collagens in the supernatant. (newyorkstemcelltherapy.com)
  • To discover all the future advances in chondrogenesis from hiPSCs and the development of novel therapies for articular cartilage degeneration, stay tuned to the Stem Cells Portal ! (stemcellsportal.com)
  • Migration and chondrogenesis of human subchondral cortico-spongious progenitor cells (SPCs) are the key steps in the repair of microfracture-induced articular cartilage defects. (mdpi.com)
  • This study demonstrated that semi-interpenetrating network parameters influence not only extracellular matrix content, but also the deposition of the matrix molecules by hMSCs undergoing chondrogenesis. (duke.edu)
  • However, mechanisms mediating control of its expression during chondrogenesis are not known. (wiley.com)
  • While successful in vitro induction of chondrogenesis with improved biochemical characteristics were obtained from hiPS cells, the working mechanisms in the implantation of hiPS cells and strategies for further improvement of in vivo cartilage repair with hiPS cells should be investigated in future studies. (bmj.com)
  • In particular, it will examine the influence of the cells' origin on the requirements for the induction of chondrogenesis and on the phenotype achieved by the cells after differentiation. (biomedcentral.com)
  • SCRG1 (Stimulator Of Chondrogenesis 1) is a Protein Coding gene. (genecards.org)
  • TGF-β will act as a stimulator of chondrogenesis, and an inhibitor of osteoblastic differentiation, by blocking the Runx2 factor through Smad3 activation. (wikipedia.org)
  • GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis. (ox.ac.uk)
  • This study demonstrated that the rhCII hydrogel functions as a xeno-free platform for BM-MSC chondrogenesis, although the process is delayed. (eur.nl)
  • Bone morphogenetic proteins are growth factors released during embryonic development to induce condensation and determination of cells, during chondrogenesis. (wikipedia.org)
  • We observed that heterotopic bone formation continued through postnatal day 28, whereas heterotopic chondrogenesis lasted only through the embryonic period. (springer.com)
  • To determine the effect of high YAP activity on chondrogenesis, C3H10T1/2 MSC-like cells were transduced with human (h)YAP and treated in micromass with bone morphogenetic protein-2 (BMP-2). (biomedcentral.com)
  • Previously, we have reported that the spliced isoform of XBP1 (XBP1s) is a crucial inducer in the BMP2 signal pathway and is involved in BMP2-triggered chondrogenesis and bone formation. (biologists.org)
  • Upon ectopic stimulation of BMP signaling, monocyte depletion leads to an enhanced contribution of ECs chondrogenesis and to ectopic bone formation, with increased bone volume and density, that is reversed by ACVR1/SMAD pathway inhibitor dipyridamole. (figshare.com)
  • We report here that BMP signaling is essential for multiple aspects of early chondrogenesis. (pnas.org)
  • mice develop a severe and generalized chondrodysplasia, demonstrating overlapping functions for BMPR1A and BMPR1B during early chondrogenesis. (pnas.org)
  • This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. (nature.com)
  • These findings suggest that chondroblastoma is derived from a mesenchymal cell undergoing chondrogenesis via active growth-plate signaling pathways (see Endochondral ossification). (wikipedia.org)
  • However, Bmpr1b null mice exhibit a restricted skeletal phenotype with defects confined to phalangeal elements, suggesting either overlapping functions or a more prominent role for BMPR1A during chondrogenesis in mice ( 9 , 10 ). (pnas.org)
  • Micromass civilizations set up from C3L10T1/2 cells are an appealing program to research chondrogenesis because these cells perform not really automatically differentiate under regular lifestyle circumstances. (cylch.org)
  • In the present study, it was investigated how changes in metabolites are implicated in ATP oscillations during chondrogenesis by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). CE-TOF-MS detected 93 cationic and 109 anionic compounds derived from known metabolic pathways. (hindawi.com)
  • However, the in vivo role of BMP signaling during chondrogenesis has been unclear. (pnas.org)
  • Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. (jci.org)
  • The chondrogenesis potential of SPCs with or without stimulation of either Fn or BMP-2 were studied by immunochemical staining and gene expression analysis. (mdpi.com)