Transforming growth factor-β1에 의한 연골세포와 제 2형 교원질의 상호 작용에서 교원질 수용체의 역할

Abstract

Purpose : The physiologic response of chondrocytes to maintenance of the matrix and response to injury likely involves signaling from multiple sources. The purposes of this study were to determine the molecular nature of collagen receptors involved in physiologic modulation. Materials and Methods : An alginate bead culture system was utilized to which exogenous type II collagen was added. We examined DNA and proteoglycan synthesis after blocking the cell surface with antibodies to anchorin CII and β1 integrin, and with cyclic RGD peptides. Results : The inclusion of type II collagen results in an alteration of integrin expression with a down-regulation of α2. The response of the chondrocyte to TGF-β1 can be modulated by the inclusion of exogenous type II collagen. The modulation of DNA and proteoglycan synthesis was blocked by the treatment of anti-β1 integrin antibody (4B4) or by cyclic RGD containing peptides. These events occur at concentrations that block cell adhesion to type II collagen. Anti-anchorin antibodies had no effect on the modulation by type II collagen. Conclusion : These results suggest that type II collagen binding by chondrocytes at least in part occurs through the β1 integrin. This binding results in modulation of the cell response to TGF-β1. This modulation may serve to provide physiologic specificity to the cytokine-signaling cascade.