Cartilage oligomeric matrix protein/thrombospondin 5 (COMP/ TSP5) is a major component of the extracellular matrix of the musculoskeletal system. Although COMP/TSP5 abnormalities are associated with several pathological conditions, its normal function remains unclear. This study was undertaken to delineate the function(s) of COMP/TSP5 in cartilage, especially regarding its interaction with chondrocytes. We show that COMP/TSP5 can support chondrocyte attachment and that the RGD sequence in COMP/ TSP5 and the integrin receptors ␣5␤1 and ␣V␤3 on the chondrocytes are involved in mediating this attachment. The interactions of COMP/TSP5 with the integrins are dependent on COMP/TSP5 conformation. Chondrocyte attachment to COMP/TSP5 in the calcium-replete conformation was inhibited by function-blocking integrin ␣5 and ␤1 antibodies, suggesting the involvement of the ␣5␤1 integrin. Under this condition, a function-blocking antibody against ␣V␤3 did not have any effect on cell attachment. On the other hand, chondrocyte attachment to reduced COMP/TSP5 was instead sensitive to ␣V␤3 function-blocking antibodies, suggesting that COMP/TSP5 mediates attachment through chondrocyte ␣V␤3 integrin under this condition. Cell attachment to reduced COMP/TSP5 was not inhibited by ␤1 antibodies. These data indicate that COMP/TSP5 in different conformations can utilize different integrin receptors. These results are the first to demonstrate that COMP/TSP5 can mediate chondrocyte attachment through interactions with integrins. Through these interactions, COMP/ TSP5 may be able to regulate cellular activities and respond to environment in the surrounding cartilage matrix.Cartilage oligomeric matrix protein (COMP), 2 also known as thrombospondin 5 (TSP5), is an abundant extracellular matrix protein that has been shown to exist in tissues of the musculoskeletal system including cartilage, tendon, ligament, and synovium (1-7). Immunohistochemistry studies of COMP/TSP5 distribution in cartilage have revealed specific temporal and spatial patterns, and COMP/TSP5 can be found in cartilage at sites both in proximity to chondrocytes in the pericellular matrix and away from the cells in the territorial and interterritorial matrix (8 -10). In fetal cartilage, COMP/TSP5 exists in the pericellular matrix, especially in the growth cartilage adjacent to the primary ossification center. In adult articular cartilage, COMP/TSP5 is found at higher levels in the interterritorial matrix, with stronger staining in the deeper zone (8 -10).The importance of COMP/TSP5 is suggested by its association with several pathological conditions. Compared with normal cartilage, the levels and patterns of COMP/TSP5 expression were found to change in cartilage of osteoarthritis and rheumatoid arthritis patients, and COMP/TSP5 in serum and synovial fluid has been suggested as a biomarker for these conditions (11-13). The importance of COMP/ TSP5 to cartilage structure and function is further underscored by findings that COMP/TSP5 mutations lead to human skeletal dysplasias, p...

Our results demonstrate the expression of COMP in both the AF and NP of the IVD. COMP is a component of the extracellular matrix of AF and NP, with a lamellar distribution pattern in the AF. Our data suggest that COMP may play a role in the normal structure of IVD.