25-Hydroxy- and 1 alpha, 25-Dihydroxycholecalciferol Have Greater Potencies than 25-Hydroxy- and 1 alpha, 25-Dihydroxyergocalciferol in Modulating Cultured Human and Mouse Osteoblast Activities

作者：Zarei Allahdad; Hulley Philippa A; Sabokbar Afsie; Javaid M Kassim; Morovat Alireza^*

来源：PLos One, 2016, 11(11): e0165462.

DOI：10.1371/journal.pone.0165462

Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D-3) and 25-hydroxyergocalciferol (25(OH)D-2) in man, the effects of these and their 1 alpha-hydroxylated forms (1,25(OH)(2)D-3 and 1,25(OH)(2)D-2) on cellular activity of vitamin D-responsive cells have hardly been compared. We studied differences in the effects of these metabolites on cell number, gene transcription, protein expression and mineralisation of cultured human bone marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3 osteoblasts. 50-1000 nM 25(OH) and 0.05-10 nM 1,25(OH)(2) metabolites were used. At high concentrations, 25(OH)D-2/D-3 and 1,25(OH)(2)D-2/D-3 suppressed cell number in both human and mouse cells. The suppression was greater with cholecalciferol (D-3) metabolites than with those of ergocalciferol (D-2). In both cell types, 25(OH)D-2 and 25(OH)D-3 increased the expression of osteopontin, osteocalcin, collagen-1, receptor activator of nuclear factor kappa-B ligand, vitamin D receptor, CYP24A1 and CYP27B1 genes. Whereas there was little or no difference between the effects of 25(OH)D-2 and 25(OH)D-3 in hBMSCs, differences were observed in the magnitude of the effects of these metabolites on the expression of most studied genes in 2T3 cells. Alkaline phosphatase (ALP) activity was increased by 25(OH)D-2/D-3 and 1,25(OH)(2)D-2/D-3 in hBMSC and 2T3 cells, and the increase was greater with the D-3 metabolites at high concentrations. In hBMSCs, mineralisation was also increased by 25 (OH)D-2/D-3 and 1,25(OH)(2)D-2/D-3 at high concentrations, with D-3 metabolites exerting a greater influence. In 2T3 cells, the effects of these compounds on mineralisation were stimulatory at low concentrations and inhibitory when high concentrations were used. The suppression at high concentrations was greater with the D-3 metabolites. These findings suggest that there are differences in the effects of 25-hydroxy and 1 alpha, 25(OH)(2) metabolites of D-3 and D-2 on human preosteoblasts and mouse osteoblasts, with the D-3 metabolites being more potent in suppressing cell number, increasing ALP activity and influencing mineralisation.

• 出版日期2016-11-28