Satellite cells are muscle stem cells that differentiate into myoblasts and then myocytes. Normally quiescent in adult muscle, satellite cells can be induced to proliferate for regeneration of muscle in response to injury. Our previous work on mice with myocyte-specific deletion of the vitamin D receptor (mVDR) found that these mice had abnormal muscle function and physiology. In this study, we used mice with deletion of VDR in satellite cells (sVDR) to investigate whether vitamin D signalling is important for muscle regeneration and repair after acute injury.
Floxed VDR mice were bred with mice expressing Cre-recombinase driven by the Pax7 promoter to generate sVDR mice and their floxed control (FC) littermates. Pax7 is expressed in satellite cells after birth. Notexin (0.1μg/mL), a myotoxin, was injected into the left tibialis anterior (TA) muscle of 6-months old female sVDR mice. The contralateral TA was injected with 0.9% saline and served as control in each mouse. Mice were euthanised after 10 days.
At 10 days, saline-injected TA in sVDRs were of similar size to FC. However, notexin treated muscles from sVDR mice were 22% smaller (P=0.0004). Notably, notexin-treated TA in FCs were 15% heavier than their matching saline-control TA (P=0.02). This effect was not observed in the sVDR mice. Assessing the size distribution of myofibres in TA, notexin treated TA in control mice had a higher population of myofibres with larger cross-sectional area (FC=5.57% vs KO=0.99%, P=0.03), and an increased proportion of fibres containing centralised nuclei (FC=59.9% vs KO=47.3%, P=0.02).
Overall, these results demonstrate an important role for vitamin D in muscle regeneration. Centralised nuclei are indicative of muscle fibres undergoing repair. Together, the larger sized myofibres and higher number of centralised myonuclei in FC mice suggest further progression of repair in muscles with normal vitamin D signalling.