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Abstract

Growing evidence suggests that intracellular vitamin D receptors are present in skeletal muscle tissue mediating vitamin D hormone response. The aim of the work reported here was to investigate the in situ expression of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Intraoperative periarticular muscle biopsies were taken from 20 female orthopaedic patients (17 middle-aged and elderly patients receiving total hip arthroplasty due to osteoarthritis of the hip or an osteoporotic hip fracture and 3 young patients who received back surgery). The immunohistological distribution of the vitamin D3 receptor was investigated using a monoclonal rat antibody to the receptor (Clone Nr. 9A7). The receptor-positive nuclei were quantified by counting 500 nuclei per biopsy. Strong intranuclear immunostaining of the vitamin D receptor was detected in human muscle cells. Biopsies of hip patients had significantly fewer receptor-positive nuclei compared to those of back surgery patients (Mann-Whitney U-test: p = 0.0025). VDR expression (number of antigen-positive nuclei) was significantly correlated with age (coefficient of correlation = 0.46; p = 0.005), but not with 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels. The data clearly demonstrate presence of nuclear 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle. To our knowledge this is the first in situ detection of the receptor in human skeletal muscle. The difference in the expression of the receptor between hip and spinal muscle biopsies might be explained by age or location. Further research is needed in order to evaluate whether vitamin D3 receptor expression in human skeletal muscle is age-dependent and varies between different muscles.

Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial

“…Muscle tissues have highly specific nuclear receptors for 1,25-[OH]2D [8]. In the present study, we found improvement, by vitamin D, of type II fiber atrophy in stroke patients who had deficient levels of serum 25-OHD before the therapy.…”

“…In a randomized controlled trial, vitamin D reduced fractures within 8–12 weeks of the treatment, and this is consistent with the benefit on muscle strength [7]. Skeletal muscle is known to express specific receptors for 1,25-dihydroxyvitamin D (1,25-[OH]2D) [8]. …”

“…The effect of vitamin D on muscle strength may be explained by its direct effects on muscle tissues [8,23,24,25]. These effects may be mediated by de novo protein synthesis, affecting muscle cell growth [26].…”

Vitamin D deficiency is associated with increased fecal incontinence symptoms

“…Vitamin D has been shown to increase skeletal muscle cell proliferation and muscle fiber size in vitro, 13,23 therefore it is biologically plausible for vitamin D serum levels to affect skeletal muscle efficiency through binding to the vitamin D receptor resulting in muscle growth. 13,23 This hypothesis may explain a potential contribution to the mechanism behind our observation of increased odds of vitamin D deficiency in women with fecal incontinence symptoms compared to controls.…”

Vitamin D treatment protects against and reverses oxidative stress induced muscle proteolysis

“…Muscle is one such target organ 10 for vitamin D and VDR is reported to be expressed in human muscle 11 tissue [3,4]. Vitamin D deficiency has been associated with muscle 12 weakness and falls in humans [5,6].…”