Cartilage Oligomeric Matrix Protein: Major component of chondrocyte EXTRACELLULAR MATRIX of various tissues including bone, tendon, ligament, SYNOVIUM and blood vessels. It binds MATRILIN PROTEINS and is associated with development of cartilage and bone.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.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).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,, MIM#100800, April 20, 2001)Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Osteochondrodysplasias: Abnormal development of cartilage and bone.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.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.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.Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.Chondrocytes: Polymorphic cells that form cartilage.Collagen Type II: A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.Synovial Fluid: The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.Integrin-Binding Sialoprotein: A highly glycosylated and sulfated phosphoprotein that is found almost exclusively in mineralized connective tissues. It is an extracellular matrix protein that binds to hydroxyapatite through polyglutamic acid sequences and mediates cell attachment through an RGD sequence.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.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Thrombospondins: A family of related, adhesive glycoproteins which are synthesized, secreted, and incorporated into the extracellular matrix of a variety of cells, including alpha granules of platelets following thrombin activation and endothelial cells. They interact with a number of BLOOD COAGULATION FACTORS and anticoagulant factors. Five distinct forms have been identified, thrombospondin 1, -2, -3, -4, and cartilage oligomeric matrix protein (COMP). They are involved in cell adhesion, platelet aggregation, cell proliferation, angiogenesis, tumor metastasis, VASCULAR SMOOTH MUSCLE growth, and tissue repair.Knee Joint: A synovial hinge connection formed between the bones of the FEMUR; TIBIA; and PATELLA.Osteoarthritis, Knee: Noninflammatory degenerative disease of the knee joint consisting of three large categories: conditions that block normal synchronous movement, conditions that produce abnormal pathways of motion, and conditions that cause stress concentration resulting in changes to articular cartilage. (Crenshaw, Campbell's Operative Orthopaedics, 8th ed, p2019)Collagen Type XII: A fibril-associated collagen found in many tissues bearing high tensile stress, such as TENDONS and LIGAMENTS. It is comprised of a trimer of three identical alpha1(XII) chains.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.Chondrosarcoma: A slowly growing malignant neoplasm derived from cartilage cells, occurring most frequently in pelvic bones or near the ends of long bones, in middle-aged and old people. Most chondrosarcomas arise de novo, but some may develop in a preexisting benign cartilaginous lesion or in patients with ENCHONDROMATOSIS. (Stedman, 25th ed)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).Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.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.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.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Tendons: Fibrous bands or cords of CONNECTIVE TISSUE at the ends of SKELETAL MUSCLE FIBERS that serve to attach the MUSCLES to bones and other structures.Knee Injuries: Injuries to the knee or the knee joint.Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.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.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Cartilage Diseases: Pathological processes involving the chondral tissue (CARTILAGE).Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.ArchivesBiological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).Synovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. (Dorland, 27th ed)Wrist Joint: The joint that is formed by the distal end of the RADIUS, the articular disc of the distal radioulnar joint, and the proximal row of CARPAL BONES; (SCAPHOID BONE; LUNATE BONE; triquetral bone).Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.

Enhancement of cell adhesion and spreading by a cartilage-specific noncollagenous protein, cartilage matrix protein (CMP/Matrilin-1), via integrin alpha1beta1. (1/201)

Cartilage matrix protein (CMP; also known as matrilin-1), one of the major noncollagenous proteins in most cartilages, binds to aggrecan and type II collagen. We examined the effect of CMP on the adhesion of chondrocytes and fibroblasts using CMP-coated dishes. The CMP coating at 10-20 micrograms/ml enhanced the adhesion and spreading of rabbit growth plate, resting and articular chondrocytes, and fibroblasts and human epiphyseal chondrocytes and MRC5 fibroblasts. The effect of CMP on the spreading of chondrocytes was synergistically increased by native, but not heated, type II collagen (gelatin). The monoclonal antibody to integrin alpha1 or beta1 abolished CMP-induced cell adhesion and spreading, whereas the antibody to integrin alpha2, alpha3, alpha5, beta2, alpha5beta1, or alphaVbeta5 had little effect on cell adhesion or spreading. The antibody to integrin alpha1, but not to other subunits, coprecipitated 125I-CMP that was added to MRC5 cell lysates, indicating the association of CMP with the integrin alpha1 subunit. Unlabeled CMP competed for the binding to integrin alpha1 with 125I-CMP. These findings suggest that CMP is a potent adhesion factor for chondrocytes, particularly in the presence of type II collagen, and that integrin alpha1beta1 is involved in CMP-mediated cell adhesion and spreading. Since CMP is expressed almost exclusively in cartilage, this adhesion factor, unlike fibronectin or laminin, may play a special role in the development and remodeling of cartilage.  (+info)

Production of cartilage oligomeric matrix protein (COMP) by cultured human dermal and synovial fibroblasts. (2/201)

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a large disulfide-linked pentameric protein. Each of its five subunits is approximately 100,000 Da in molecular weight. COMP was originally identified and characterized in cartilage and it has been considered a marker of cartilage metabolism because it is currently thought not to be present in other joint tissues, except for tendon. To confirm the tissue specificity of COMP expression we examined cultured human dermal fibroblasts, human foreskin fibroblasts, and normal human synovial cells for the synthesis of COMP in culture. METHOD: Normal synovial cells and normal human dermal foreskin fibroblasts were isolated from the corresponding tissues by sequential enzymatic digestions and cultured in media containing 10% fetal bovine serum until confluent. During the final 24 h of culture, the cells were labeled with 35S-methionine and 35S-cysteine in serum- and cysteine/methionine-free medium. The newly synthesized COMP molecules were immunoprecipitated from the culture media with a COMP-specific polyclonal antiserum, or with monoclonal antibodies or affinity-purified COMP antibodies. The immunoprecipitated COMP was analyzed by electrophoresis in 5.5% polyacrylamide gels. For other experiments, synovial cells cultured from the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were similarly examined. RESULTS: A comparison of the amounts of COMP produced by each cell type (corrected for the DNA content) revealed that synovial cells produced > or = 9 times more COMP than chondrocytes or dermal fibroblasts. COMP could be easily detected by immunoprecipitation in all cell types. Electrophoretic analysis revealed a distinct band with an apparent MW of 115-120 kDa in samples from each of the three cell types, regardless of the antibody used. COMP expression in cultures of synoviocytes derived from OA and RA patients showed that OA and RA synovial cells produced similar amounts of monomeric COMP of identical size to those COMP monomers produced by normal synovial cells. The addition of TGF-beta to these cultures resulted in an increase in COMP production in normal, OA and RA synovial cells (45, 116 and 115% respectively). CONCLUSION: These studies demonstrate that substantial amounts of COMP are produced by several mesenchymal cells including synoviocytes and dermal fibroblasts. These findings raise important concerns regarding the utility of measurements of COMP levels in serum or in synovial fluid as markers of articular cartilage degradation because of the likelihood that a substantial proportion of COMP or COMP fragments present in serum or synovial fluid may be produced by cells other than articular chondrocytes.  (+info)

Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project. (3/201)

OBJECTIVE: To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA. METHODS: Serum samples and knee and hip radiographs were obtained at a baseline evaluation as part of the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. A total of 291 Caucasian participants were randomly selected for COMP analysis, 143 patients with radiographic knee OA (Kellgren/Lawrence [K/L] grade > or = 2) and 148 controls with neither hip nor knee OA (K/L grade 0), evenly distributed by age and gender. COMP was quantified by competitive enzyme-linked immunosorbent assay with monoclonal antibody 17-C10. The natural log-transformed COMP data were analyzed using general linear models. RESULTS: Serum COMP levels were significantly elevated (P = 0.0001) in the age > or = 65 group (mean +/- SD 1,302.1 +/- 496.7 ng/ml) versus the age 45-54 and age 55-64 groups (1,058.1 +/- 432.4 and 1,038.6 +/- 313.3, respectively). Serum COMP levels of the OA group were significantly higher than those of the control group (1,208.57 +/- 487.47 ng/ml versus 1,061.83 +/- 370.58 ng/ml; P = 0.0093). Serum COMP levels also increased significantly with knee OA K/L grade (P = 0.0047), knee OA laterality (P = 0.0043), and number of knee and hip joints involved (P = 0.0001). There was no significant difference in serum COMP levels by gender or obesity. CONCLUSION: We demonstrate that in a population-based sample, serum COMP levels can distinguish an OA-affected subgroup from an unaffected subgroup and can reflect disease severity and multiple joint involvement in OA.  (+info)

A cartilage oligomeric matrix protein mutation associated with pseudoachondroplasia changes the structural and functional properties of the type 3 domain. (4/201)

Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin family of extracellular matrix glycoproteins. All members of the family contain a highly conserved region of thrombospondin type 3 sequence repeats that bind calcium. A mutation in COMP previously identified in a patient with pseudoachondroplasia resulted in abnormal sequestration of COMP in distinctive rER vesicles. The mutation, Asp-446 --> Asn, is located in the type 3 repeats of the molecule. This region was expressed in a mammalian culture with and without the mutation to study the structural or functional properties associated with the mutation. The biophysical parameters of the mutant peptide were compared with those of the wild type and revealed the following difference: secondary structural analysis by circular dichroism showed more alpha-helix content in the wild-type peptides. The calcium binding properties of the two peptides were significantly different; there were 17 calcium ions bound/wild-type COMP3 peptide compared with 8/mutant peptide. In addition, wild-type COMP3 had a higher affinity for calcium and bound calcium more cooperatively. Calcium bound by the wild-type peptide was reflected in a structural change as indicted by velocity sedimentation. Thus, the effect of the COMP mutation appears to profoundly alter the calcium binding properties and may account for the difference observed in the structure of the type 3 domain. Furthermore, the highly cooperative binding of calcium to COMP3 suggests that these type 3 sequence repeats form a single protein domain, the thrombospondin type 3 domain.  (+info)

Autoreactivity against matrilin-1 in a patient with relapsing polychondritis. (5/201)

Relapsing polychondritis (RP) is a rare inflammatory disease of cartilage. Chondritis of the auricular, nasal, and tracheal cartilages predominates in this disease, suggesting a response to a tissue-specific antigen. One potential antigen is matrilin-1, a cartilage matrix protein found uniquely in the tracheal, auricular, and nasal cartilage of adults. We describe herein a patient with RP who had both a humoral and a cellular immune response directed toward the cartilage matrix protein matrilin-1.  (+info)

Molecular cloning and expression patterns of mouse cartilage oligomeric matrix protein gene. (6/201)

OBJECTIVE: To develop transgenic mice harboring mutations in the COMP gene as animal models for pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), autosomal dominant disorders characterized by early onset osteoarthritis and epiphyseal abnormalities. As a first step in generating a mouse model for COMP mutations, we have cloned the cDNA of mouse COMP and examined its tissue expression pattern. DESIGN: Total mRNA was isolated from the skeletal tissues of newborn C57BL/6j mice and used as a template for oligo(dT) first-strand cDNA synthesis. The cDNA was used for PCR amplification of COMP using three oligonucleotide primer pairs designed from the published rat COMP cDNA sequence. Nested PCR was used to complete the sequence between the amplified fragments. The entire cDNA was sequenced and the expression pattern of the corresponding transcripts examined by Northern hybridizations. RESULTS: A full-length COMP cDNA was isolated. Analysis showed that the entire translated region of the mouse COMP gene is 2268 bp and the derived amino acid sequence shows 90% homology to human COMP. Of eight adult mouse non-cartilage tissues tested, COMP expression was detected only in testis.  (+info)

Pseudoachondroplastic dysplasia: an Iowa review from human to mouse. (7/201)

Lamellar inclusions of the rough endoplasmic reticulum in growth plate chondrocytes, first identified (1972) in the Department of Orthopaedic Surgery, University of Iowa, has become the cytochemical hallmark for the pseudoachondroplastic dysplasia (PSACH) phenotype, linking an endoplasmic reticulum storage disorder with the osteochondrodysplasia. Since this original observation, great advances have been made, leading to the molecular understanding of this altered longitudinal bone growth anomaly. A PSACH canine model suggested that abatement of cumulative vertical growth of growth plate chondrocytes seen in PSACH results from (1) altered extracellular matrix constraints for horizontal growth and (2) uncoupling of endochondral and perichondral growth that causes metaphyseal flaring. PSACH, an autosomal dominant disease, is linked to mutation of the cartilage oligomeric matrix protein (COMP) gene. Amino acid substitutions, deletions, or additions is proposed to alter COMP structure that cause its retention in the rough endoplasmic reticulum of growth plate chondrocytes, leading to (1) compositional and structural change of the extracellular matrix, and (2) altered cellular proliferation and volume expansion. Normal growth and development occurs in COMP gene knockout mice that do not synthesis COMP, demonstrating that a mutant COMP, not absence of COMP, is required for the PSACH phenotype. The mechanism by which mutant COMP induces a PSACH phenotype remains to be elucidated. At the University of Iowa a cell culture system has been developed whereby mutant COMP transgenes are introduced into chondrocytes and the expressed product COMP is retained in the endoplasmic reticulum. This readily manipulated system makes it possible to decipher systematically the system's cellular secretory processing pathway, in order to clarify the mechanism(s) by which the mutant COMP is retained within the endoplasmic reticulum. Concurrent with this is the development of transgenic mice expressing the mutant COMP used in the cell culture system. This will make it possible to establish that expression of a human PSACH-linked mutant COMP will produce a PSACH phenotype. A PSACH animal model will provide a means to characterize the mechanism of altered longitudinal bone growth and to test gene therapy approaches for correcting the anomaly.  (+info)

Cartilage oligomeric matrix protein is a calcium-binding protein, and a mutation in its type 3 repeats causes conformational changes. (8/201)

Mutations in residues in the type 3 calcium-binding repeats and COOH-terminal globular region of cartilage oligomeric matrix protein (COMP) lead to two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. It has been hypothesized that these mutations cause COMP to misfold and to be retained in the endoplasmic reticulum. However, this hypothesis is not supported by previous reports that COMP, when purified in the presence of EDTA, shows no obvious difference in electron microscopic appearance in the presence or absence of calcium ions. Since this discrepancy may be due to the removal of calcium during purification, we have expressed wild-type COMP and the most common mutant form found in pseudoachondroplasia, MUT3, using a mammalian expression system and have purified both proteins in the presence of calcium. Both proteins are expressed as pentamers. Direct calcium binding experiments demonstrate that wild-type COMP, when purified in the presence of calcium, is a calcium-binding protein. Rotary shadowing electron microscopy and limited trypsin digestion at various calcium concentrations show that there are conformational changes associated with calcium binding to COMP. Whereas COMP exists in a more compact conformation in the presence of calcium, it shows a more extended conformation when calcium is removed. MUT3, with a single aspartic acid deletion in the type 3 repeats, binds less calcium and presents an intermediate conformation between the calcium-replete and calcium-depleted forms of COMP. In conclusion, we show that a single mutation in the type 3 repeats of COMP causes the mutant protein to misfold. Our data demonstrate the importance of calcium binding to the structure of COMP and provide a plausible explanation for the observation that mutations in the type 3 repeats and COOH-terminal globular region lead to pseudoachondroplasia.  (+info)

  • This study aims to investigate the regulation of expression of Cartilage oligomeric matrix protein (COMP), which is predominately expressed by chondrocytes and functions to organize the extracellular matrix. (
  • We then compared the temporal expression of COMP with the well-characterized cartilage-specific Type II collagen (Col2a1), and their response to transforming growth factor (TGF)β and Sox trio (Sox5, 6, and 9) stimulation. (
  • B) COMP protein is detected earlier than Col2a1 during chondrogenesis. (
  • The amounts of COMP and Col2a1 proteins recovered from cells and their associated extracellular matrix were detected by Western blot. (
  • To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA. (
  • Chondrocytes and synovial cells synthesize Cartilage Oligomeric Matrix Protein (COMP) when activated by proinflammatory cytokines. (
  • To test the hypothesis that physiological cyclic loading during a 30-min walking exercise causes an increase in serum cartilage oligomeric matrix protein (COMP) concentration in a healthy population. (
  • The immediate response points to a diffusion time of COMP fragments from cartilage to the blood of 30 min or less. (
  • We measured gene expression by microarray analysis in primary cultured human chondrocytes treated with either GH or IGF-I. One of the genes found to be up-regulated by both GH and IGF-I was that encoding cartilage oligomeric matrix protein (COMP). (
  • Disulfide bound complexes of lubricin and cartilage oligomeric matrix protein (COMP) have recently been identified in arthritic synovial fluid suggesting they may be lost from the cartilage surface in osteoarthritis and inflammatory arthritis. (
  • This investigation was undertaken to localise COMP-lubricin complexes within cartilage and investigate if other cartilage proteins are involved in anchoring lubricin to the joint. (
  • Immunohistochemical analysis of human cartilage biopsies showed lubricin and COMP co-localise to the cartilage surface. (
  • COMP knockout mice, however, presented with a lubricin layer on the articular cartilage leading to the further investigation of additional lubricin binding mechanisms. (
  • Proximity ligation assays (PLA) on human cartilage biopsies was used to localise additional lubricin binding partners and demonstrated that lubricin bound COMP, but also fibronectin and collagen II on the cartilage surface. (
  • Overall, COMP, fibronectin and collagen II bind lubricin, exposed on the articular cartilage surface suggesting they may be involved in maintaining essential boundary lubrication. (
  • and C reactive protein, cartilage oligomeric matrix protein (COMP), rheumatoid factor (RF) (IgG, IgA, and IgM subtypes), antibodies against cyclic citrullinated peptide (anti-CCP), and antibodies against interleukin 1α (anti-IL1α), analysed by immunoassays. (
  • Early determination of anti-CCP, IgA RF, anti-IL-1α, ESR, C reactive protein, and COMP predicted the development of joint damage in hands and feet in this cohort. (
  • Comparative analysis with collagen type II distinguishes cartilage oligomeric matrix protein as a primary TGFβ-responsive gene. (
  • Živanović S, Petrović Rackov L, Živanović A, Jevtić M, Nikolić S, Kocić S. Cartilage Oligomeric Matrix Protein - inflammation biomarker in knee osteoarthritis. (
  • The crystal structure of the signature domain of cartilage oligomeric matrix protein. (
  • Gentaur Molecular :Biovend \ Human, Cartilage Oligomeric Matrix Protein CHO , Rec. (
  • their genotyping in conjunction with the assessment of classical protein molecular markers is recommended. (
  • In fact, members of both of these families of secreted multidomain proteins can interact with numerous other ECM components and thus shape or regulate the molecular environment. (
  • Investigador postdoctoral en el laboratorio del Dr. Carlos López-Otín en el departamento de Bioquímica y Biología molecular de la Universidad de Oviedo. (
  • We have focused on endogenous molecular clocks based on spontaneous posttranslational protein modification by deamidation-the nonenzymatic hydrolysis of the amide group on the side chains of asparagine (Asn, N) and glutamine (Gln, Q) to yield aspartate (Asp, D) and glutamate (Glu, E) ( 5 ), respectively. (
  • The turnover of cartilage proteins is particularly suited to study using protein molecular clocks because many cartilage proteins are long lived and therefore susceptible to accumulation of many types of age-related posttranslational nonenzymatic protein amino acid modifications ( 13 - 15 ). (
  • Turnover of insoluble collagen has been suggested to be very limited in human adult cartilage. (
  • The goal of this study was to explore protein turnover in articular cartilage from human lower limb joints. (
  • Although humans have a limited natural regenerative capacity, evidenced by the ability to regrow distal portions of amputated digits during childhood ( 2 ), by the carbon-14 ( 14 C) bomb pulse method, turnover of insoluble collagen (residual after hyaluronidase and trypsin digestion) was suggested to be very limited in human adult cartilage and Achilles tendon ( 3 , 4 ). (
  • Thrombospondin-1 (TSP1) plays an indirect role in collagen homeostasis through interactions with matrix metalloproteinases and transforming growth factor-β1 (TGF-β1). (
  • In that regard, a molecule known as thrombospondin-1 (TSP-1) is important because it is the first naturally occurring protein inhibitor of angiogenesis to be identified. (
  • The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi. (
  • In general, the main components of the ECM are macromolecules and fibrous proteins as well as a wide variety of enzymes, including proteases, which are involved in processes such as the maturation, assembly, and renewal of ECM components. (
  • fibrous proteins of two functional types which have structural and adhesive types. (
  • We are currently working to identify signaling molecules and other membrane proteins that collaborate with CD36 to inhibit endothelial cell function. (
  • Folgueras A, Pendás AM, Sanchez LM, López-Otín C. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. (
  • We have previously reported that matrix metalloproteinases MMP-2, MMP-9, and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. (
  • The present study identifies a tumor-specific fingerprinting pattern, based on the detection of matrix metalloproteinases in urine of cancer patients, which may noninvasively facilitate identification of cancer presence and type. (
  • Furthermore, macrophages and CD4 + T cells were the most prominent cell types in inflammatory infiltrates of the tracheal cartilage. (
  • Unlike highly regenerative animals, such as axolotls, humans are believed to be unable to counteract cumulative damage, such as repetitive joint use and injury that lead to the breakdown of cartilage and the development of osteoarthritis. (
  • Humans are also believed to be unable to counteract the cumulative damage of repetitive joint use or one substantial, usually sports- or trauma-related, injury that leads to the breakdown of cartilage and the development of osteoarthritis (OA). (
  • Increased serum levels of cartilage oligomeric matrix protein in patients with psoriasis vulgaris: a marker for unknown peripheral joint involvement? (
  • This finding has significant implications for cellular functions including autophagy, protein synthesis, and potentially cellular viability. (
  • Rough ER, the portion of ER displaying ribosomes, is the network of membranous tubules within cells associated with protein and lipid synthesis and export. (
  • Skeletal dysplasias, also known as osteochondrodysplasias, are a heterogeneous group of heritable disorders characterized by abnormalities of cartilage and bone growth, resulting in abnormal shape and size of the skeleton and disproportion of the long bones, spine, and head. (
  • In the ECM, especially the basement membrane, the multidomain proteins perlecan, agrin, and COLXVIII are the main proteins to which heparan sulfate attaches [ 7 ]. (
  • Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins (BIRC3, BIRC2, BIRC5 and XIAP). (
  • Cartilage oligomeric matrix protein protects cells against death by elevating members of the IAP family of survival proteins. (