High-Throughput Gene and Protein Analysis Revealed the Response of Disc Cells to Vitamin D, Depending on the VDR FokI Variants

Abstract

Vitamin D showed a protective effect on intervertebral disc degeneration (IDD) although conflicting evidence is reported. An explanation could be due to the presence of the FokI functional variant in the vitamin D receptor (VDR), observed as associated with spine pathologies. The present study was aimed at investigating—through high-throughput gene and protein analysis—the response of human disc cells to vitamin D, depending on the VDR FokI variants. The presence of FokI VDR polymorphism was determined in disc cells from patients with discopathy. 1,25(OH)2D3 was administered to the cells with or without interleukin 1 beta (IL-1β). Microarray, protein arrays, and multiplex protein analysis were performed. In both FokI genotypes (FF and Ff), vitamin D upregulated metabolic genes of collagen. In FF cells, the hormone promoted the matrix proteins synthesis and a downregulation of enzymes involved in matrix catabolism, whereas Ff cells behaved oppositely. In FF cells, inflammation seems to hamper the synthetic activity mediated by vitamin D. Angiogenic markers were upregulated in FF cells, along with hypertrophic markers, some of them upregulated also in Ff cells after vitamin D treatment. Higher inflammatory protein modulation after vitamin D treatment was observed in inflammatory condition. These findings would help to clarify the clinical potential of vitamin D supplementation in patients affected by IDD.

Constitutive and conditional gene knockout mice for the study of intervertebral disc degeneration: Current status, decision considerations, and future possibilities

“…As we all know, vitamin D needs to be hydroxylated a second time in the kidneys for it to function. The direct and indirect relationship between vitamin D and disc degeneration has already been confirmed 150 . Therefore, the target gene specifically knocked out in Col2 Cre mice for IVD research can also affect the function of the kidney.…”

“…The direct and indirect relationship between vitamin D and disc degeneration has already been confirmed. 150 Therefore, the target gene specifically knocked out in Col2 Cre mice for IVD research can also affect the function of the kidney. Defective kidney function may influence disc degeneration through ways other than the knockout gene.…”

Inflammatory priming with IL-1β promotes the immunomodulatory behavior of adipose derived stem cells

“…A huge panel of genes of interest (maximum 3,000 genes, including at least five replicates for each gene) was selected and analyzed through a custom gene expression microarray designed through Agilent Technologies ( https://earray.chem.agilent.com/earray/ , date of access 12 February 2018) ( De Luca et al, 2020a ; De Luca et al, 2020b ; Colombini et al, 2021b ).…”

Progress of Gene‐Functionalized Regenerative Material Repair Intervertebral Disc Degeneration

“…VDR gene encodes vitamin D receptor protein and controls the autophagy level of NPCs. [40,41] In addition, the genes encoding inflammatory factors are closely related to IDD-related inflammation, matrix destruction, cell senescence, autophagy, apoptosis, and other pathological processes. [42,43] The central genes of IVD clock control, ARNTL and CLOCK, encode clock proteins, and BMAL1, respectively.…”

“…[12] For example, hydrogels based on ultra-pure alginate, hyaluronic acid (HA), methylcellulose, and gelatin NPs have been thoroughly researched for their ability to support mesenchymal stem cells (MSCs) and repair interdiscs. [69,70] Coding genes Noncoding genes ECM metabolism ADAMTS [137,138] miR-106b-5p, [144] miR-3d, [145] miR-193a-3p, [146] miR-338-3p, [147] miR-150, [148] miR-499a-5p [149] VDR [40,41] Aggrecan [139,140] Collagen-II [35,141,142] MMPs [29,39] LncR-00917, [150] LncR-HOTAIR, [151] LncR-OIP5-AS1, [152] miR-93, [153] miR-137, [154] miR-874-3p [155] TIMP [37] miR-199a-5p, [107] miR-15a, [156] miR-217, [157] Lnc00641, [158] miR-26a-5p, [159] circR-GRB10, [160] miR-155, [161] miR-30d, [145] circERCC, [162] circGPATCH6L, [163] circR-CIDN, [164] circSPG21, [165] miR-145, [166] miR-338-3p, [147] miR-24-3p, [167] miR-573 [168] Inflammation level IL-1β…”