Modulation of integrin-mediated attachment of chondrocytes to extracellular matrix proteins by cations, retinoic acid, and transforming growth factor beta.
Articular cartilage chondrocytes are surrounded by an abundant extracellular matrix (ECM) and the interactions between chondrocytes and ECM proteins have important effects on chondrocyte function. In this study, attachment assays were used to examine integrin-mediated attachment of chondrocytes to fibronectin, matrix Gla protein (MGP), and type II collagen. A cyclic peptide containing the Arg-Gly-Asp integrin recognition sequence was capable of blocking attachment of chondrocytes to all three ECM proteins including collagen. Cations were required for chondrocyte attachment and provided a mechanism to differentially regulate attachment to ECM proteins. Mg2+ and Mn2+ supported attachment to all three ECM proteins but Ca2+ did not support attachment to collagen and was less effective than Mg2+ or Mn2+ in chondrocyte attachment to MGP. Treatment of chondrocytes with retinoic acid for the first 3 days of culture, prior to use in attachment assays, resulted in a decrease in the attachment to collagen but not to fibronectin or MGP. Seven days of retinoic acid treatment resulted in decreased attachment to fibronectin, MGP, and collagen. Treatment with 100 pM TGF-beta for 18 h stimulated attachment to all three proteins. TGF-beta treatment was able to at least partially overcome the inhibitory effects of retinoic acid. These results demonstrate several important mechanisms by which chondrocyte-ECM interactions may be modulated. The differential effects of retinoic acid and TGF-beta on attachment correlate with their known effects on matrix synthesis, which suggests a link between matrix synthesis and integrin expression in chondrocytes.
Loeser
R F
RF
Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D002412:Cations / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D016023:Integrins / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D000097568:Matrix Gla Protein
D002118:Calcium; D002135:Calcium-Binding Proteins; D002412:Cations; D003094:Collagen; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D008274:Magnesium; D008345:Manganese; D009842:Oligopeptides; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D000097568:Matrix Gla Protein; C047981:arginyl-glycyl-aspartic acid