Differential regulation of lubricin/superficial zone protein by transforming growth factor β/bone morphogenetic protein superfamily members in articular chondrocytes and synoviocytes

Abstract

Objective To investigate the role of transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) superfamily members on accumulation of superficial zone protein (SZP) in articular chondrocytes and synoviocytes. Methods Chondrocytes and synoviocytes were isolated from articular cartilage and synovium from calf stifle joints and cultured as monolayers in serum‐free chemically defined medium. Articular chondrocytes were isolated from 3 distinct zones of the cartilage: superficial, middle, and deep. Accumulation of SZP in the culture medium in response to various members of the TGFβ/BMP superfamily was demonstrated by immunoblotting and quantified by enzyme‐linked immunosorbent assay. Results TGFβ stimulated SZP accumulation in both superficial zone chondrocytes and synoviocytes. The 3 isoforms of TGFβ elicited a similar dose response. Inhibition of TGFβ receptor type I kinase by the specific inhibitor SB431542 abolished the TGFβ‐stimulated accumulation of SZP. BMPs up‐regulated SZP accumulation in the superficial zone; however, the magnitude of the effects was not as great as was observed with TGFβ. There was an additive action between TGFβ and BMP on SZP accumulation. The response of synoviocytes to BMP was stronger than that of superficial zone chondrocytes. Activin up‐regulated SZP accumulation in synoviocytes, but not in chondrocytes. Conclusion TGFβ is a critical regulator of SZP accumulation in both superficial zone articular chondrocytes and synoviocytes. TGFβ and BMP have an additive effect. Synoviocytes are more sensitive to BMP family members and activins than are superficial zone articular chondrocytes. Thus, regulation of SZP accumulation by TGFβ /BMP superfamily members is regulated differently in articular chondrocytes and synoviocytes.