Vitamin D and Skeletal Muscle: Novel Effects on Morphology and Morphogenesis

Abstract

Since the discovery of vitamin D in the 1920’s, research has focused predominantly on its effects in bone and mineral homeostasis. Emerging evidence supports broader effects of vitamin D in modulating the cell cycle, tissue development and the response to injury. At a tissue level, skeletal muscle underpins the emerging concept that vitamin D exerts effects beyond bone. This thesis addressed this issue by examining four different models of murine muscle and by employing a range of established and novel techniques. The vitamin D receptor (VDR) was clearly detected in skeletal muscle and VDR activation led to an intriguing anabolic effect with doubling in the size of cultured muscle cells. Mice lacking VDR displayed significantly lighter muscles, smaller muscle fibres, reduced strength and reduced muscle uptake of 3H-25(OH)D3 compared to wild-type (WT) mice. Mice with diet-induced vitamin D deficiency displayed reduced grip strength that progressed with age and activation of atrophy genes. These data support anabolic and functional roles of vitamin D/VDR in muscle. On the basis of these findings, the vitamin D pathway holds promise in the treatment of muscle disorders and in enhancing muscle repair.