1,25(OH)2vitamin D3 enhances myogenic differentiation by modulating the expression of key angiogenic growth factors and angiogenic inhibitors in C2C12 skeletal muscle cells
The Journal of Steroid Biochemistry and Molecular Biology Volume 133, January 2013, Pages 1–11 Leah A. Garcia
Vitamin D is mostly recognized for its regulation of calcium homeostasis in relation to the intestine, kidney, and bone. Although clinical studies have linked vitamin D with increased muscle function and strength, little is known of its underlying molecular mechanism. We recently
demonstrated that 1,25-D3 exerts a direct pro-myogenic effect on skeletal muscle cells;
this has provoked our investigation of 1,25-D's effect on angiogenesis, a vital process for new capillary development and tissue repair. In this study, we examined the mechanism by which 1,25-D3 modulates key angiogenic growth factors and angiogenic inhibitors. C2C12 myoblasts were incubated with 100 n.M 1,25-D3 or placebo for 1, 4 and 10 days. At the end of the respective incubation time, total RNA was isolated for PCR arrays and for qRT-PCR. Total proteins were isolated for Western blots and proteome profiler arrays. The addition of 1,25-D3 to C2C12 myoblasts increased VEGFa and FGF-1: two pro-angiogenic growth factors that promote neo-vascularization and tissue regeneration, and decreased FGF-2 and TIMP-3: two myogenic and/or angiogenic inhibitors. Our previous study demonstrated that 1,25-D3 altered IGF-I/II expression, consistent with the observed changes in VEGFa and FGF-2 expression. These results extend our previous findings and demonstrate the
modulation of angiogenesis which may be an additional mechanism by which 1,25-D3 promotes myogenesis.
This study supports the mechanistic rationale for assessing the administration of vitamin D and/or vitamin D analogs to treat select muscle disorders and may also provide an alternative solution for therapies that directly manipulate VEGF and FGF's to promote angiogenesis.
