E-Poster 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

Mice with muscle stem cell (satellite cell) deletion of the vitamin D receptor (sVDR) are weak and have small myocytes (#43)

Jennifer Chen 1 , Christian M Girgis 1 2 3 , Jessie Zhou 1 , Jenny E Gunton 1 2 3
  1. The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia
  2. Faculty of Health and Medicine, University of Sydney, Sydney, NSW, Australia
  3. Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia

Vitamin D deficiency is prevalent, especially amongst older persons and some ethic groups. It is associated with an increased risk of falls and sarcopenia. Our group demonstrated mice with myocyte-specific deletion of the vitamin D receptor (mVDR) are weak with small muscles and have fewer, larger myocytes. The large myocytes contrast findings in whole-body VDR knockout mice which have smaller myocytes. This study aimed to determine the effect of deleting VDR in satellite cells on muscle strength and myocyte size.

Floxed VDR mice were crossed with paired box 7 (Pax7)-Cre mice to generate sVDR mice. Muscle development during the embryonic stages is predominantly Pax3 driven; Pax7 has a greater postnatal role. Thus, initial myocytes are expected to be normal, and only newer myocytes should derive from Pax7+ VDR-null cells. Muscle function was examined using forelimb grip strength tests and treadmill endurance tests in which mice were encouraged to run until fatigued. At sacrifice, muscles were collected and myofibre histology was quantified.

While body weight was similar between the two groups, sVDR mice displayed consistently weaker grip strength compared to their floxed control siblings as they aged (P<0.01 by ANOVA with repeated measures for both sexes). The time and distance spent running on the treadmill before the onset of fatigue was similar in both genotypes. At cull, wet muscle mass in the sVDR mice was not different to their control group siblings. However, the average myofiber cross-sectional area was smaller in sVDR mice (P<0.01).

These results suggest that satellite cell-specific VDR deletion has different effects on muscle function and physiology in contrast to skeletal myocyte deletion.  Future experiments will test whether there are any changes in muscle fibre typing, and measure the expression of genes in apoptotic and cell cycle pathways. 

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