Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins.
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 alpha5beta1 and alphaVbeta3 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 alpha5 and beta1 antibodies, suggesting the involvement of the alpha5beta1 integrin. Under this condition, a function-blocking antibody against alphaVbeta3 did not have any effect on cell attachment. On the other hand, chondrocyte attachment to reduced COMP/TSP5 was instead sensitive to alphaVbeta3 function-blocking antibodies, suggesting that COMP/TSP5 mediates attachment through chondrocyte alphaVbeta3 integrin under this condition. Cell attachment to reduced COMP/TSP5 was not inhibited by beta1 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.
Chen
Faye Hui
FH
Department of Orthopaedic Surgery, Columbia University, New York, New York 10032, USA.
Thomas
Ashby O
AO
Hecht
Jacqueline T
JT
Goldring
Mary B
MB
Lawler
Jack
J
D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein; D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D064235:Matrilin Proteins; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D011485:Protein Binding; D011487:Protein Conformation
D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D016023:Integrins; D064235:Matrilin Proteins; D010455:Peptides; C577553:TSP5 protein, human; D003513:Cycloheximide; D002118:Calcium