Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts

Cesare, Paul E. Di; Fang, Carrie; Leslie, Michael; Tulli, Hermina M.; Perris, Roberto; Carlson, Cathy S.

doi:10.1002/jor.1100180506

Cited by 82 publications

(71 citation statements)

References 25 publications

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“…45 COMP has been reported to be expressed by both embryonic and adult osteoblasts. 46 Immunostaining and in situ hybridization in published reports have shown the presence of COMP in the bone collar, the newly formed bone near the growth plate and in the diaphysis of a 21-day human fetus. 46 All the genes encoding ECM proteins that were upregulated as shown in Table 1 (except COMP) were significantly upregulated when 2-week ECM scaffold culture was compared with 4-week control scaffold culture (Table 3).…”

Section: Ecm Componentsmentioning

confidence: 99%

Biomimetic Extracellular Matrix-Incorporated Scaffold Induces Osteogenic Gene Expression in Human Marrow Stromal Cells

Ravindran

Gao

Kotecha

et al. 2012

Tissue Engineering Part A

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Engineering biomaterials mimicking the biofunctionality of the extracellular matrix (ECM) is important in instructing and eliciting cell response. The native ECM is highly dynamic and has been shown to support cellular attachment, migration, and differentiation. The advantage of synthesizing an ECM-based biomaterial is that it mimics the native cellular environment. However, the ECM has tissue-specific composition and patterned arrangement. In this study, we have employed biomimetic strategies to develop a novel collagen/chitosan template that is embedded with the native ECM of differentiating human marrow stromal cells (HMSCs) to facilitate osteoblast differentiation. The scaffold was characterized for substrate stiffness by magnetic resonance imaging and nanoindentation and by immunohistochemical analysis for the presence of key ECM proteins. Gene expression analysis showed that the ECM scaffold supported osteogenic differentiation of undifferentiated HMSCs as significant changes were observed in the expression levels of growth factors, transcription factors, proteases, receptors, and ECM proteins. Finally, we demonstrate that the scaffold had the ability to nucleate calcium phosphate polymorphs to form a mineralized matrix. The results from this study suggest that the threedimensional native ECM scaffold directly controls cell behavior and supports the osteogenic differentiation of mesenchymal stem cells.

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Section: Ecm Componentsmentioning

confidence: 99%

Biomimetic Extracellular Matrix-Incorporated Scaffold Induces Osteogenic Gene Expression in Human Marrow Stromal Cells

Ravindran

Gao

Kotecha

et al. 2012

Tissue Engineering Part A

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“…To examine whether divalent cations were involved in this association, 5 mM Ca 2+ were added to one set of binding buffer. The bound proteins were denatured in sample buffer and separated by 12% SDS-PAGE, and COMP protein was detected by Western blotting with polyclonal rabbit anti-COMP antiserum (4,21,45).…”

Section: In Vitro Gst Pulldown Assaymentioning

confidence: 99%

“…To examine COMP degradation by full-length ADAMTS-7 and to investigate the zinc ion concentration dependence of the intact enzyme, purified COMP (200 nM) was incubated with the cell lysates prepared from Sf9 insect cells infected with either control or ADAMTS-7 bacluovirus in the presence of lower (0.1 mM) or higher (2 mM) levels of ZnCl 2 as well as in the absence of Zn 2+ by addition of 5 mM EDTA in a digestion buffer (50 mM Tris-HCl, 100 mM NaCl, 5 mM CaCl 2 , and 0.05% Brij-35, pH 7.5) at 37°C for 12 h. The digested nonreduced products were resolved by 10% SDS-PAGE, and intact COMP and COMP fragments were detected by Western blotting with polyclonal rabbit anti-COMP antiserum, as described previously (4,21,45).…”

Section: In Vitro Digestion Assaymentioning

confidence: 99%

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ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Liu¹,

et al. 2006

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Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. The physiological enzyme(s) that degrade COMP, however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search for proteins that associate with COMP to identify an interaction partner that might degrade it. One screen using the epidermal growth factor (EGF) domain of COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595 amino acids, and this protein exhibits higher expression in the musculoskeletal tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with the other three functional domains of COMP, whereas the four C-terminal TSP motifs of ADAMTS-7 are required and sufficient for association with COMP. The recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn 2+ and appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and synovium of patients with rheumatoid arthritis is significantly increased as compared to normal cartilage and synovium. ADAMTS-7 is the first metalloproteinase found to bind directly to and degrade COMP.-Liu, C., Kong, W., Ilalov, K., Yu, S., Xu, K., Prazak, L., Fajardo, M., Sehgal, B., Di Cesare, P. E. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. The extracellular matrix (ECM) of cartilage consists of several types of collagens, proteoglycans, and other noncollagenous macromolecules, all of which interact to form a highly specialized connective tissue (1). Early extracellular cartilage matrix degeneration in arthritis is the result of the action of degradative enzymes. As the severity of arthritis progresses, the synthesis and secretion of matrix-degrading enzymes markedly increase (2). The control 1 These authors contributed equally to this work.

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“…For immunoblotting, the proteins were transferred to a nitrocellulose membrane and incubated with appropriate antibodies diluted in TBS. Bound antibodies were detected by luminescence using peroxidase-conjugated secondary antibodies (Dako), 3- 24), rabbit anti-matrilin 3, rabbit antimatrilin 1, and rabbit anti-matrilin 4 (1:1,000 dilution; see ref. 25), rabbit antiaggrecan (1:1,000 dilution; Chemicon item no.…”

Section: Methodsmentioning

confidence: 99%

Abnormal bone quality in cartilage oligomeric matrix protein and matrilin 3 double‐deficient mice caused by increased tissue inhibitor of metalloproteinases 3 deposition and delayed aggrecan degradation

Groma¹,

Xin²,

Grskovic³

et al. 2012

Arthritis & Rheumatism

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Objective. Cartilage oligomeric matrix protein (COMP) and matrilin 3 are extracellular matrix proteins that are abundant in cartilage. As adaptor molecules, both proteins bridge and stabilize macromolecular networks consisting of fibrillar collagens and proteoglycans. Mutations in the genes coding for COMP and matrilin 3 have been linked to human chondrodysplasias, while in mice, deficiency in COMP or matrilin 3 does not cause any pronounced skeletal abnormalities. Given the similar functions of COMP and matrilin 3 in the assembly and stabilization of the extracellular matrix, our aim was to determine whether these proteins could functionally compensate for each other.Methods. To assess this putative redundancy of COMP and matrilin 3, we generated COMP/matrilin 3 double-deficient mice and performed an in-depth analysis of their skeletal development.Results. At the newborn stage, the overall skeletal morphology of the double mutants was normal, but at 1 month of age, the long bones were shortened and the total body length reduced. Peripheral quantitative computed tomography revealed increased metaphyseal trabecular bone mineral density in the femora. Moreover, the degradation of aggrecan in the cartilage remnants in the metaphyseal trabecular bone was delayed, paralleled by increased deposition of tissue inhibitor of metalloproteinases 3 (TIMP-3). The structure and morphology of the growth plate were grossly normal, but in the center, focal closures were observed, a phenotype very similar to that described in matrix metalloproteinase 13 (MMP-13)-deficient mice.Conclusion. We propose that a lack of COMP and matrilin 3 leads to increased deposition of TIMP-3, which causes partial inactivation of MMPs, including MMP-13, a mechanism that would explain the similarities in phenotype between COMP/matrilin 3 doubledeficient and MMP-13-deficient mice.The 2 major components of the cartilage extracellular matrix are the fibrillar collagens and the large hyaluronan-binding proteoglycan aggrecan. A variety of different proteins, including cartilage oligomeric matrix protein (COMP) and matrilin 3, modulate the assembly and structure of the extracellular matrix, generating complex functional networks. Matrilins are noncollagenous oligomeric extracellular matrix proteins with similar domain structure and function. Matrilin 1 and matrilin 3 are found almost exclusively in cartilage, while matrilin 2 and matrilin 4 have a broader tissue distribution. Subunits of matrilins 1 and 4 mainly form homotrimers, whereas subunits of matrilins 2 and 3 are found in homotetramers (1,2). In addition, heterotrimers consisting of matrilin 1 and matrilin 3 subunits can form. Matrilins function as adaptor proteins in the extracellular matrix and connect collagen fibrils with each other and with aggrecan (2). Via their von Willebrand type A-like domain, matrilins interact with several other matrix components, including COMP (3),

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Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts

Cited by 82 publications

References 25 publications

Biomimetic Extracellular Matrix-Incorporated Scaffold Induces Osteogenic Gene Expression in Human Marrow Stromal Cells

Biomimetic Extracellular Matrix-Incorporated Scaffold Induces Osteogenic Gene Expression in Human Marrow Stromal Cells

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Abnormal bone quality in cartilage oligomeric matrix protein and matrilin 3 double‐deficient mice caused by increased tissue inhibitor of metalloproteinases 3 deposition and delayed aggrecan degradation

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