Abstract
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.
Highlights
Skeletal muscle is one of largest tissues in the body, and its volume and function are well maintained during life until middle age
We demonstrated that a high concentration of active vitamin D, 1α,25(OH)2 D3, affected terminal differentiation of myoblasts
Previous studies have reported that this inhibitory effect on myogenic regulatory factors (MRFs) expression resulted in the inhibition of terminal differentiation, because myogenin is necessary for myotube formation [30]
Summary
Skeletal muscle is one of largest tissues in the body, and its volume and function are well maintained during life until middle age. From middle age, the maintenance system for muscle homeostasis gradually declines, resulting in sarcopenia, an age-related muscular phenotype with evident loss of muscle mass and strength [1]. Sarcopenia is currently recognized as an independent age-related muscle disorder and is diagnosed in about 5–10% of individuals over 65 years of age [2,3]. Humoral changes resulting from decreased circulation of some vitamins, cytokines, and growth factors are known to be contributing factors in the occurrence of sarcopenia in elderlies [4]. The level of vitamin D in circulation is considered to be a sarcopenia-related factor; this is because there is some evidence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
