[C.sub.2][C.sub.12] myoblast/osteoblast transdifferentiation steps enhanced by epigenetic inhibition of BMP2 endocytosis

[C.sub.2][C.sub.12] myoblast/osteoblast transdifferentiation steps enhanced by epigenetic inhibition of BMP2 endocytosis. Am J Physiol Cell Physiol 283: C235-C243, 2002. First published February 27, 2002; 10.1152/ajpcell.00234. 2001.--We investigated the modulation of critical transcriptional steps of [C.sub.2][C.sub.12] myoblast/osteoblast transdifferentiation triggered by the bone morphogenetic protein 2 (BMP2) signaling protein, in response to epigenetic inhibition of the endocytotic internalization of exogenous BMP2. BMP2 endocytosis was inhibited chemically with polyethylene glycol-50 (PEG-Cho1) and cyclodextrin and mechanically by mild hyposmotic treatment. BMP2-dependent nuclear translocation of the mother against Dpp (Smad1) transcription factor was ten times faster if BMP2 endocytosis was inhibited. Smad1-dependent expression of the JunB gene, the first transcriptional step in myoblast dedifferentiation, was increased by a factor of three to four. JunB-dependent levels of myogenin repression, one of the critical markers of terminal myoblastic differentiation, was amplified by a factor of three. Smad1-dependent levels of alkaline phosphatase expression, one of the [C.sub.2][C.sub.12] osteoblast differentiation markers, were 3.5 to 5 times higher. The same behavior was observed for osteopontin, the other [C.sub.2][C.sub.12] osteoblast differentiation marker. These results suggest that the cell genome could 'sense' tissue mechanical deformations by mechanical inhibition of signaling protein endocytosis, thereby translating mechanical strains into transcription events involved in cell differentiation. morphogen cell internalization; mechanotranscription transduction; embryogenesis.