Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation.

摘要: The proteins of the hedgehog (Hh) family regulate various aspects development. Recently, members this have been shown to skeletal formation in vertebrates and control both chondrocyte osteoblast differentiation. In present study, we analyzed effect Sonic (Shh) on osteoblastic adipocytic commitment/differentiation. Recombinant N-terminal Shh (N-Shh) significantly increased percentage pluripotent mesenchymal cell lines C3H10T1/2 ST2 calvaria cells responding bone morphogenetic protein 2 (BMP-2), terms commitment as assessed by measuring alkaline phosphatase (ALP) activity. This synergistic was mediated, at least partly, through positive modulation transcriptional output BMPs via Smad signaling. Furthermore, N-Shh found abolish differentiation presence or absence BMP-2. A short treatment with sufficient dramatically reduce levels adipocytic-related transcription factors C/EBPalpha PPARgamma cultures. Given inverse relationship between marrow adipocytes osteoblasts aging, agonists Hh signaling pathway might constitute potential drugs for preventing and/or treating osteopenic disorders.