?Comparative actions of 1α,25(OH)2D3-glycosides and synthetic 1α,25(OH)2D3 during miogénesis?

AMUSQUIVAR A; A. PAULA IRAZOQUI; GONZALEZ PARDO V; BUITRAGO C

Congreso; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2016

We previously reported that the steroid hormone 1,25(OH)2-vitamin D3 [1,25D] promotes muscle cell proliferation and differentiation in murine skeletal muscle cells. In this work we present data indicating that the vitamin D receptor (VDR) is involved in cell cycle modulation promoting differentiation in C2C12 cell line. When VDR was knocked down (80%) by a shRNA against this receptor, the activation of p38 MAPK by 1,25D was abolished. Furthermore, the up-regulation of cyclin D3 and cyclin inhibitors (p21Waf1/Cip1 and p27Kip1) by the hormone also occurred in a VDR dependent manner. 1,25D-induced G0/G1 phase arrest was evidenced by flow cytometry assays. At same time, the hormone prompted an increase in myogenin levels only when VDR was expressed. In C2C12 wild type cells, expression of cyclin D3, p21Waf1/Cip1 and p27Kip1 triggered by 1,25D was not observed in presence of SB203580, a specific inhibitor of p38 MAPK activation. P38 MAPK was also required in the 1,25D -promoted CREB transcription factor expression. The results suggest that VDR is involved in p38 MAPK activation by 1,25D, which modulates the cellular cycle in skeletal muscle cells. Further studies are required to understand the complete 1,25(OH)2-vitamin D3 regulation of myogenesis.