Vitamin D's Effect on the Proliferation and Inflammation of Human Intervertebral Disc Cells in Relation to the Functional Vitamin D Receptor Gene FokI Polymorphism.

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 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 cells. Regarding the metabolic effects, in 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 genotype were the most responsive to vitamin D in the upregulation of catabolic markers. In addition, in contrast to the genotype, vitamin D downregulated the vitamin D-dependent signaling pathway in inflamed cells, counteracting the inflammation-mediated catabolic effects. In conclusion, 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.