title: Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Columbia University, New York, New York 10032, USA.
authors.forename: Faye Hui
authors.initials: FH
authors.lastname: Chen
authors.forename: Ashby O
authors.initials: AO
authors.lastname: Thomas
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
authors.forename: Jack
authors.initials: J
authors.lastname: Lawler
mesh_terms: 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
chemical_list: 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