Vitamin D deficiency is strongly associated with falls, muscle weakness, and sarcopenia. Our previous studies demonstrated whole-body vitamin D receptor (VDR) deletion in mice reduces their grip strength and endurance.
Aim: This project investigates the effects of myocyte-specific Vitamin D receptor deletion (mVDR) on muscle regeneration and function.
Methods: Floxed VDR mice and human skeletal actin Cre-recombinase mice were bred to generate mVDR mice and their floxed control (FC) littermates were used as controls. Ten-month old males (n = 11-13/group) were injected with Notexin in their right tibialis anterior (TA) to induce myocyte death. The left TA was injected with saline-control. Mice were monitored for 28 days to assess regeneration. Treadmill endurance tests (day 14) and forelimb grip strength (day 26) were performed to investigate muscle function. Promethion cages were used to measure voluntary wheel running. Quadriceps and TAs were weighed and collected upon cull.
Results: mVDR body weights did not differ significantly to FC, but they showed decreased grip strength (rmANOVA, p<0.01). However, there were no significant differences in endurance-distance or voluntary wheel-running. At 28 days, the notexin-treated TA mass in mVDRs was 25% heavier than their left-TA control (p=0.031) and 18% heavier than notexin-treated FC mice TA (p=0.04), suggesting possible oedema in the regenerating muscle. Preliminary histological analysis of mVDR notexin-treated muscles showed a high proportion of central nuclei and ongoing myocyte regeneration.
Conclusion: mVDR showed decreased grip strength and increased TA weight after a notexin-model of muscle injury and regeneration. However, there were no significant differences in endurance or voluntary wheel running suggesting muscle function effects were resolved by completion of the study. Further histological assessment will be performed to investigate increased TA mass and muscle morphology.