Clinical trials involving in patients with
osteoporosis have reported that activated
vitamin D3 (1α,25(
OH)2D3,
calcitriol) can prevent falling by acting on the skeletal muscles. However, pharmacological mechanisms of 1α,25(
OH)2D3 with respect to skeletal muscle
hypertrophy or
atrophy are still poorly understood. Therefore, we examined changes in the expression of several related genes in human myotubes to test whether 1α,25(
OH)2D3 influences
hypertrophy and
atrophy of skeletal muscle. Myotubes treated with 1α,25(
OH)2D3 increased
interleukin-6 (IL-6) expression and inhibited expression of
tumor necrosis factor alpha (TNF-α), whereas the expression of
insulin-like growth factor-1 (IGF-1) that is involved in muscle
hypertrophy was not affected. However, 1α,25(
OH)2D3 treatment significantly inhibited the expression of
muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1),
ubiquitin ligases involved in
muscle atrophy. The analysis of pathways using microarray data suggested that 1α,25(
OH)2D3 upregulates AKT-1 by inhibiting the expression of
protein phosphatase 2 (PP2A), a
phosphatase acting on AKT-1, in the
phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, thereby inhibiting the expression of
ubiquitin ligases. Thus, this study showed that 1α,25(
OH)2D3 might have an inhibitory effect on the expression of MAFbx and MuRF1 in skeletal muscle and a suppressive effect on muscle degradation in patients with
osteoporosis.