Chen, Faye HuiThomas, Ashby O.Hecht, Jacqueline T.Goldring, Mary B.Lawler, Jack2019-10-052005Chen, Faye Hui, Ashby O. Thomas, Jacqueline T. Hecht, Mary B. Goldring, and Jack Lawler. 2005. “Cartilage Oligomeric Matrix Protein/Thrombospondin 5 Supports Chondrocyte Attachment through Interaction with Integrins.” Journal of Biological Chemistry 280 (38): 32655–61. https://doi.org/10.1074/jbc.m504778200.0021-92581083-351Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483164Cartilage 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 alpha 5 beta 1 and alpha V beta 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 alpha 5 and beta 1 antibodies, suggesting the involvement of the alpha 5 beta 1 integrin. Under this condition, a function- blocking antibody against alpha V beta 3 did not have any effect on cell attachment. On the other hand, chondrocyte attachment to reduced COMP/ TSP5 was instead sensitive to alpha V beta 3 function- blocking antibodies, suggesting that COMP/ TSP5 mediates attachment through chondrocyte alpha V beta 3 integrin under this condition. Cell attachment to reduced COMP/ TSP5 was not inhibited by beta 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.en-USJournal Article2019-10-0510.1074/jbc.M504778200