Vitamin D, a fat-soluble
vitamin, is an important nutrient for tissue homeostasis and is recently gaining attention for its role in
sarcopenia. Although several studies have focused on the role of
vitamin D in muscle homeostasis, the molecular mechanism underlying its action on skeletal muscle remains unclear. This study investigated the role of
vitamin D in myogenesis and muscle fiber maintenance in an immortalized mouse myogenic cell line. A high concentration of active
vitamin D, 1α,25(
OH)2D3, decreased the expression of
myogenic regulatory factors (MRFs), myf5 and
myogenin in proliferating myoblasts. In addition, high concentration of
vitamin D reduced myoblast-to-myoblast and myoblast-to-myotube fusion through the inhibition of Tmem8c (myomaker) and Gm7325 (myomerger), which encode muscle-specific fusion-related
micropeptides. A similar inhibitory effect of
vitamin D was also observed in immortalized human myogenic cells. A high concentration of
vitamin D also induced
hypertrophy of multinucleated myotubes by stimulating
protein anabolism. The results from this study indicated that
vitamin D had both positive and negative effects on muscle homeostasis, such as in muscle regeneration and myofiber maintenance. Elderly individuals face a higher risk of falling and suffering fractures; hence, administration of
vitamin D for treating fractures in the elderly could actually promote fusion impairment and, consequently, severe defects in muscle regeneration. Therefore, our results suggest that
vitamin D replacement
therapy should be used for prevention of age-related muscle loss, rather than for treatment of
sarcopenia.