P38 MAPK AND VDR ARE REQUIRED IN 1,25(OH)2-VITAMIN D3-DEPENDENT CELL CYCLE MODULATION IN SKELETAL MUSCLE CELLS

A. PAULA IRAZOQUI; BOLAND RICARDO; BUITRAGO CLAUDIA GRACIELA

Workshop; 17 th Workshop of Vitamin D; 2014

We previously reported that 1,25(OH)2-vitamin D3 (1,25D) induces rapid p38 MAPK activation in a VDR-dependent manner in proliferative C2C12 myoblast cells. Recently, it was evidenced that the VDR is required in modulation of the cell cycle. We now present data indicating that p38 MAPK also participates in the mechanism by which the 1,25D mediates muscle cell proliferation and differentiation. In C2C12 cells the VDR was knocked down by a shRNA and p38 MAPK inhibited using SB-203580. The hormone prompts a peak of S-phase followed by an arrest in G0/G1-phase, evidenced by flow cytometry, which was dependent on p38 MAPK activation in wild type cells. Moreover, 1,25D induces an increase in expression of cyclin D3, and CDK inhibitors, p21Waf1/Cip1 and p27Kip1 during G0/G1 arrest. In all these events, the activation of p38 MAPK was required. At the same time, a 1,25D -dependent acute increase in myogenin expression was observed when p38 MAPK was activated; indicating that G0/G1 arrest of cells is a pro-differentiative event. In conclusion, VDR and p38 MAPK are involved in control of cellular cycle by 1,25D in skeletal muscle cells, forming part of the mechanism underlying hormone regulation of myogenesis.