THE VDR IS INVOLVED IN 1,25(OH)2-VITAMIN D3-DEPENDENT EXPRESSION OF CYCLINS D1 AND D3 AND ARREST OF G0/G1 PHASE OF PROLIFERATING SKELETAL MUSCLE CELLS

A. PAULA IRAZOQUI; BUITRAGO C; BOLAND R

Workshop; Workshop of Vitamin D; 2013

We previously reported that the VDR participates in non-transcriptional events triggered by 1,25(OH)2-vitamin D3 [1,25D] in skeletal muscle cells. Thus, the hormone induces rapid activation of Src, ERK 1/2 p38 MAPK and Akt in a VDR-dependent manner in C2C12 cells. In separate studies we have demonstrated that 1,25D promotes muscle cell proliferation and differentiation. In this work we present preliminary data indicating that the VDR may also play a role in the mechanism which mediates these effects. 1,25D ?induced the expression of cyclin D1 and cyclin D3, as shown by Western blot analysis. When the vitamin D receptor was knocked down (80%) by transfection of C2C12 cells with a shRNA against the VDR, the up-regulation of both cyclins by 1,25D was abolished. Cell cycle studies by flow cytometry evidenced an arrest of the G0/G1 phase after hormone stimulation, which was dependent on VDR expression. The results suggest that VDR is involved in the control of the cellular cycle by 1,25D in skeletal muscle cells although the role of the hormone- induced changes in cyclins remains to be elucidated. Further studies are required to understand 1,25(OH)2-vitamin D3 regulation of myogenesis.