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Vitamin D Inhibits Myogenic Cell Fusion and Expression of Fusogenic Genes.

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.
AuthorsTohru Hosoyama, Hiroki Iida, Minako Kawai-Takaishi, Ken Watanabe
JournalNutrients (Nutrients) Vol. 12 Issue 8 (Jul 23 2020) ISSN: 2072-6643 [Electronic] Switzerland
PMID32717927 (Publication Type: Journal Article)
Chemical References
  • Vitamin D
Topics
  • Cell Fusion
  • Cell Line
  • Cell Proliferation (drug effects)
  • Gene Expression (drug effects)
  • Humans
  • Hypertrophy
  • Muscle Development (drug effects, genetics)
  • Muscle, Skeletal (metabolism)
  • Myoblasts (drug effects, metabolism)
  • Sarcopenia
  • Vitamin D (antagonists & inhibitors)

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