Abstract
In this study, we investigated the relationship between sarcopenia (evaluated in term of fibers atrophy), vitamin d receptor protein expression and TaqI/Cdx2/FokI VDR genotypes in an Italian cohort of osteoporosis(n=44) and osteoarthritis (n=55) patients. Muscle biopsies were fixed and investigated by both immunohistochemistry (vitamin d receptor expression) and transmission electron microscopy (satellite stem cells niches). Vitamin d receptor polymorphisms were studied on DNA extracted from muscle paraffin sections. For the first time, we reported that aging differently affects the VDR activation in OA and OP patients. In particular, while in OP patients we observed a significant reduction of VDR positive myonuclei with age, no “age effect” was observed in OA patients. The frequent activation of VDR could explain the lower number of atrophic fiber that we observed in OA patients respect to OP. From genetic point of view, we showed a putative association among polymorphisms FokI and Cdx2 of VDR gene, vitamin d receptor activation and the occurrence of sarcopenia. Altogether these data open new prospective for the prevention and cure of age-related muscle disorders.
Highlights
In this study, we investigated the relationship between sarcopenia, vitamin d receptor protein expression and TaqI/Cdx2/FokI Vitamin D receptor (VDR) genotypes in an Italian cohort of osteoporosis(n=44) and osteoarthritis (n=55) patients
From genetic point of view, we showed a putative association among polymorphisms FokI and Cdx2 of VDR gene, vitamin d receptor activation and the occurrence of sarcopenia
Ling et al (2016) examined the relationship between Cdx2 polymorphism and serum 25(OH)D levels, bone mineral density (BMD) and fracture in Chinese population [29,30]. They found that the A allele in Cdx2 polymorphism in the VDR gene was associated with serum 25(OH)D levels, increased BMD and decreased risk of fracture in women [29,30]
Summary
The OP group included 44 patients with fragility hip fracture, T-score ≤−2.5 SD and K – L score from 0 to 1 (Table.). We analyzed the combination of the different genotypes of the two functional polymorphisms of the VDR genes, Cdx and FokI, in relationship with percentage of atrophic fibers evaluated in both OP and OA groups (Fig. 5D). Bischoff-Ferrari et al reported the expression of VDR in muscle tissues demonstrating that older age was significantly associated with decreased VDR expression, independent of biopsy location and serum 25(OH)D levels [18] Starting from these evidences, in this study we investigated the relationship among muscle quality, evaluated in term of percentage of atrophic fibers, VDR nuclear expression and the main VDR polymorphisms associated with OP or OA namely Cdx, TaqI and FokI. Our data highlight the prominence of VDR activity and genetic variability on muscle aging and sarcopenia typical of OA and OP patients
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