INVOLVEMENT OF ALPHA-5-BETA-1 INTEGRIN IN MATRIX INTERACTIONS AND PROLIFERATION OF CHONDROCYTES

Integrins are cell surface receptors involved in cellular processes in cluding adhesion, migration, and matrix assembly, In the present study , we analyzed the possible involvement of alpha 5 beta 1 integrin in t he regulation of chondrocyte adhesion, spreading, and proliferation, W e found that rabbit growth plate chondrocytes were able to attach to s ubstrates coated with type I collagen, type II collagen, or fibronecti n within 24 h of culture, During this time period, attachment to fibro nectin appeared to be dependent on alpha 5 beta 1 integrin, whereas ad hesion to collagens was not, By day 3 of culture, chondrocytes spread onto all the substrates tested, We found that regardless of the nature of the substrate, cell spreading was reversed by treatment with RGD p eptide or antibodies against alpha 5 beta 1 or fibronectin, indicating that cell spreading involved alpha 5 beta 1 and fibronectin endogenou sly produced and deposited by the chondrocytes themselves, Colony form ation by chondrocytes in soft agar was inhibited by treatment with RGD peptides or BIIG2, an antibody that interferes with alpha 5 beta 1 in tegrin-ligand interactions. Furthermore, DNA content was decreased by treatment with anti-fibronectin antibody in micromass culture of chond rocytes. Immunohistochemical analysis on tissue sections revealed that the alpha 5 subunit was particularly abundant in the proliferative an d hypertrophic zones of growth plate, The results of the study indicat e that alpha 5 beta 1 integrin plays multiple roles in chondrocyte beh avior and function and appears to be involved in the regulation of bot h chondrocyte-matrix interactions and proliferation.