The vitamin D receptor regulates inflammatory and regenerative responses to skeletal muscle injury — ASN Events
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  3. The vitamin D receptor regulates inflammatory and regenerative responses to skeletal muscle injury

The vitamin D receptor regulates inflammatory and regenerative responses to skeletal muscle injury (#55)

Christian M Girgis 1 , Peter Houweling 2 , Nancy Mokbel 1 , Amit Lalwani 1 , Kuan Cha 1 , Kristen Thomas 2 , Roderick J Clifton-Bligh 3 , Jenny E Gunton 1
  1. Garvan Institute, Darlinghurst, NSW, Australia
  2. Institute of Neuromuscular Research, Childrens' Hospital, Westmead, Sydney, NSW, Australia
  3. Northern Metabolic Bone Research Laboratory, Kolling Institute, Sydney, NSW, Australia

Intro: Vitamin D deficiency is associated with muscle weakness, myalgia and age-related sarcopaenia. These features may result from defects in muscle repair. However, precise mechanisms are unclear.

Aim: We examined potential roles of the vitamin D receptor (VDR) in a murine model of muscle injury.

Methods: To induce acute damage, 100 ug of Notexin (NTX), a purified venom from Australian tiger snake (Notechis scutatus scutatus), was injected in the Tibialis anterior (TA) muscle of WT and VDR knockout (KO) mice (8–12 wks). Saline was injected in the other side as control. Muscles were harvested at days 5 and 10 post-injection. Candidate genes were assessed by RT-PCR.

Results: Extensive muscle damage and inflammatory infiltrates were observed in both groups at day 5. There was a significant increase in the mass of NTX- versus saline-injected muscles in WT (15% increase, p<0.05) but not in VDR KO mice (p=0.9), suggesting oedema in WT mice alone. WT mice also displayed greater CK levels than VDR KO mice at day 5 (3433 vs 658 U/l, p<0.005). VDR mRNA and protein levels increased in WT mice following NTX injury (ie 9.2-fold increase versus saline, p<0.005). VDR KO mice displayed differences in gene expression at day 5 compared to WTs, specifically an increase in the expression of IL-6 (1.4-fold, p<0.05), an anti-inflammatory myokine, and reduced expression of TNF-alpha (0.6-fold, p<0.005). VDR KO mice displayed increased Pax7 mRNA (1.9-fold, p<0.005), a marker of satellite cell proliferation and of myogenic regulatory factors, myoD and myogenin (2.2 and 1.8-fold increase, p<0.005).

Conclusion: VDR is substantially upregulated during muscle damage due to NTX-induced injury. VDR ablation leads to reduced inflammatory response, absence of oedema at day 5 and the earlier induction of myogenic regulatory factors following severe muscle injury in mice. These data suggest that VDR plays a regulatory role in muscle repair. 

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