Expression of the vitamin D receptor in skeletal muscle: are we there yet?

Abstract

The diverse biological actions of the vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) that are beyond its contribution to the maintenance of mineral metabolism are now well recognized (1). These actions include significant roles in skin maturation, protection, and function, the immune system, cardiovascular activity, neuromuscular function, bile acid metabolism, xenobiotic detoxification, muscle activity, and hepatic function (2). They also include broad cellular growth control mechanisms that include blockade of proliferation, prodifferentiation, induced apoptosis, and other fundamental cellular processes that may be of therapeutic relevance in cancer (3). Many of these activities have been described over a span of several decades both in cultured cells of specific lineage origin and in vivo. In the latter case, these studies have made frequent use of genetic strains of mice that are either globally or tissue specifically deficient in the expression of the vitamin D receptor (VDR), the central mediator of vitamin D action in all tissues (2, 4, 5). Perhaps most importantly, the beneficial biological effects of vitamin D in many of these systems appear to have translational and clinical components as well, because clinical pathologies associated with these systems frequently correlate with vitamin D deficiency, and at least, a subset have been shown to respond positively to increased vitamin D intake (6). Accordingly, the actions of 1,25(OH)2D3 in many of these tissues in humans are generally not in dispute.