VDR INVOLVEMENT IN 1,25(OH)2-VITAMIN D3-DEPENDENT CELL CYCLE MODULATION IN SKELETAL MUSCLE CELLS

A. PAULA IRAZOQUI; BOLAND R; BUITRAGO C

Congreso; Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas y de Biología Molecular (SAIB); 2013

We previously reported that 1,25(OH)2-vitamin D3 [1,25D] promotes muscle cell proliferation and differentiation in murine skeletal muscle cells. We now 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 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. At same time, the hormone increased 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. p38 MAPK was also required for 1,25D-induced 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 clearly understand 1,25(OH)2-vitamin D3 regulation of myogenesis.