The recent discovery of the vitamin D receptor (VDR) in regenerating muscle raises the question regarding the action of vitamin D3 on skeletal muscle regeneration. To investigate the action of vitamin D3 on this process, tibialis anterior (TA) muscle of male C57BL/6 mice (10 weeks of age) was injected with 1.2% BaCl2 to induce extensive muscle injury. The bioactive form of vitamin D3 [1α,25(OH)2D3] was administered daily via intramuscular injections during regenerative phase (day 4-7 post-injury). Physiological and supraphysiological doses of 1α,25(OH)2D3 relative to 1 µg/kg muscle wet weight (MW) and mouse body weight (BW) were investigated. Muscle samples were collected on day 8 post-injury to examine proteins related to vitamin D3 metabolism (VDR, CYP24A1, and CYP27B1), satellite cell differentiation and regenerative muscle fiber formation (myogenin and EbMHC), protein synthesis signaling (Akt, p70 S6K1, 4E-BP1, and myostatin), fiber type composition (fast and slow MHCs), fibrous formation (vimentin), and angiogenesis (CD31). Administration of 1α,25(OH)2D3 at physiological and supraphysiological doses enhanced VDR expression in regenerative muscle. Moreover, CYP24A1 and vimentin expression was increased, accompanying decreased myogenin and EbMHC expression at the supraphysiological dose. However, there was no change in CYP27B1, Akt, p70 S6K1, 4E-BP1, myostatin, fast and slow MHCs, or CD31 expression at any dose investigated. Taken together, administration of 1α,25(OH)2D3 at supraphysiological dose decreased satellite cell differentiation, delayed regenerative muscle fiber formation, and increased muscular fibrosis. However, protein synthesis signaling, fiber type composition, and angiogenesis were not affected by either 1α,25(OH)2D3 administration at physiological or supraphysiological dose.
- vitamin D3
- intramuscular injection
- muscle regeneration
- muscular fibrosis
- Copyright © 2015, Journal of Applied Physiology