Abstract
Vitamin D is known to have immunomodulatory effects, is involved in osteo-cartilaginous metabolism, and may have a role in human intervertebral disc pathophysiology. Although a link between vitamin D receptor (VDR) gene variants and disc degeneration-related pathologies has been observed, its functional contribution to pathologic processes has not been assessed yet. The aim of this study was to investigate the response of disc cells to vitamin D in terms of the regulation of proliferation, metabolism, and inflammatory processes, with a particular focus on the FokI VDR genotype. However, although it was found that vitamin D had a pro-apoptotic effect regardless of genotype, an up-regulation of IL-1Ra and downregulation of IL-6 was found to be evident only in Ff cells. Regarding the metabolic effects, in Ff cells, vitamin D promoted an upregulation of the aggrecan in inflammatory conditions but did not have an effect on the expression of collagen-related markers. Moreover, cells bearing the Ff genotype were the most responsive to vitamin D in the upregulation of catabolic markers. In addition, in contrast to the FF genotype, vitamin D downregulated the vitamin D-dependent signaling pathway in inflamed Ff cells, counteracting the inflammation-mediated catabolic effects. In conclusion, Ff cells were found to be more responsive to the anti-inflammatory and catabolic effects of vitamin D, which is likely to be related to matrix remodeling.
Highlights
The involvement of the vitamin D endocrine system in the pathophysiology of the human intervertebral disc is still a topic of debate which is not fully explored
The main finding of this study is that the cells bearing the two different FokI vitamin D receptor (VDR) gene variants show some differences in response to the treatment with vitamin D, where the Ff genotype was the most responsive
Regardless of the FokI VDR genotype, vitamin D had an inhibitory effect on the proliferation and metabolic activity of the disc cells while favoring a pro-apoptotic induction on these kinds of cells, as already reported in previously published studies [1,2]
Summary
The involvement of the vitamin D endocrine system in the pathophysiology of the human intervertebral disc is still a topic of debate which is not fully explored. Few in-vitro studies have reported that vitamin D regulates proliferation, the expression of matrix genes, production of structural proteins, cytokines, and growth factors in cells obtained from the two main anatomical components of the disc, the nucleus pulposus (NP), and the annulus fibrosus (AF), and expressing the vitamin D receptor (VDR) [1,2]. The need to perform functional studies to analyze the effects of vitamin D on the fibro-cartilaginous disc and the osteo-cartilaginous endplate (CEP) resides in a number of evidences.
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