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

@entity20361 @entity14901 @entity21602 @entity19 @entity2450 @entity1184 @entity20358 @entity20360 @entity43601 @entity643 @entity8385 @entity43463 @entity20356
We investigated the effects of @entity8385 , a member of the transforming growth factor-beta superfamily, on the regulation of the chondrocyte phenotype, and we identified signaling molecules involved in this regulation. @entity8385 triggers three concomitant responses in @entity19 primary chondrocytes and chondrocytic MC615 cells. First, @entity8385 stimulates expression or synthesis of type II collagen. Second, @entity8385 induces expression of molecular markers characteristic of pre- and @entity1184 chondrocytes, such as Indian hedgehog, parathyroid hormone/parathyroid hormone-related peptide receptor, type X collagen, and alkaline phosphatase. Third, @entity8385 induces @entity2450 expression, a specific trait of osteoblasts. Constitutively active forms of transforming growth factor-beta family type I receptors and Smad proteins were overexpressed to address their role in this process. @entity20356 , @entity20358 , @entity20360 , and @entity20361 were able to reproduce the @entity1184 maturation of chondrocytes induced by @entity8385 . In addition, @entity20358 mimicked further the osteoblastic differentiation of chondrocytes induced by @entity8385 . In the presence of @entity8385 , @entity14901 , @entity21602 , and @entity43463 potentiated the @entity1184 maturation of chondrocytes, but failed to induce @entity2450 expression. @entity43601 and @entity643 impaired chondrocytic expression and osteoblastic differentiation induced by @entity8385 . Thus, our results indicate that Smad-mediated pathways are essential for the regulation of the different steps of chondrocyte and osteoblast differentiation and suggest that additional Smad-independent pathways might be activated by @entity20358 .
