Evidence for a Role of Smad6 in Bone Morphogenetic Protein Regulation of Chondrocyte Maturation

INTRODUCTION Bone Morphogenetic Proteins (BMPs) are members of the transforming growth factor-β superfamily and regulate cell growth, differentiation and development in many tissues. BMPs bind to type I and type II serine/threonine kinase receptors and transduce intracellular signals through Smad proteins. Smads can be classified into three subclasses, each with different roles in mediating signaling between plasma membrane and the nucleus. Smad1, Smad5 and Smad8 are activated by BMP receptors. These receptor-regulated Smads form complexes with the common partner Smad4 and translocate into the nucleus, where they regulate transcription of various target genes. Smad6 and Smad7 are inhibitors of TGF-β family signaling. While Smad7 inhibits both TGFand BMP mediated Smad signaling, Smad6 is specific for BMPs. The discovery of inhibitory Smads suggests the possibility of a novel functional mechanisms to modulate BMP-mediated signal transduction during chondrocyte maturation. The present study was performed to characterize the expression of Smad-6 in the cephalic sternal chondrocyte cell culture model. We find that Smad6 is differentially expressed during chondrocyte maturation and plays a functional role in chondrocyte differentiation. METHODS