Functions of transforming growth factor-beta family type I receptors and Smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes.

摘要: We investigated the effects of bone morphogenetic protein (BMP)-2, a member transforming growth factor-beta superfamily, on regulation chondrocyte phenotype, and we identified signaling molecules involved in this regulation. BMP-2 triggers three concomitant responses mouse primary chondrocytes chondrocytic MC615 cells. First, stimulates expression or synthesis type II collagen. Second, induces molecular markers characteristic pre- hypertrophic chondrocytes, such as Indian hedgehog, parathyroid hormone/parathyroid hormone-related peptide receptor, X collagen, alkaline phosphatase. Third, osteocalcin expression, specific trait osteoblasts. Constitutively active forms family I receptors Smad proteins were overexpressed to address their role process. Activin receptor-like kinase (ALK)-1, ALK-2, ALK-3, ALK-6 able reproduce maturation induced by BMP-2. In addition, ALK-2 mimicked further osteoblastic differentiation presence BMP-2, Smad1, Smad5, Smad8 potentiated but failed induce expression. Smad6 Smad7 impaired Thus, our results indicate that Smad-mediated pathways are essential for different steps osteoblast suggest additional Smad-independent might be activated ALK-2.We ALK-2.