Clinical characteristics influence in vitro action of 1,25-dihydroxyvitamin D3 in human marrow stromal cells

Zhou, Shuanhu; Glowacki, Julie; Kim, Sung Won; Hahne, Jochen; Geng, Shuo; Mueller, Stefan M.; Shen, Longxiang; Bleiberg, Ilan; LeBoff, Meryl S.

doi:10.1002/jbmr.1655

Cited by 53 publications

(46 citation statements)

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“…Some studies have described 1,25(OH) 2 D 3 as being able to increase human osteoblasts mineralization, leading to earlier and higher rate of mineral deposition [46], and able to accelerate hMSCs commitment with the subsequent osteoblast maturation [47, 48]. …”

Section: Discussionmentioning

confidence: 99%

Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues

Posa

Benedetto

Colaianni

et al. 2016

Stem Cells International

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1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D (Vit D), increases intestinal absorption of calcium and phosphate, maintaining a correct balance of bone remodeling. Vit D has an anabolic effect on the skeletal system and is key in promoting osteoblastic differentiation of human Mesenchymal Stem Cells (hMSCs) from bone marrow. MSCs can be also isolated from the immature form of the tooth, the dental bud: Dental Bud Stem Cells (DBSCs) are adult stem cells that can effectively undergo osteoblastic differentiation. In this work we investigated the effect of Vit D on DBSCs differentiation into osteoblasts. Our data demonstrate that DBSCs, cultured in an opportune osteogenic medium, differentiate into osteoblast-like cells; Vit D treatment stimulates their osteoblastic features, increasing the expression of typical markers of osteoblastogenesis like RUNX2 and Collagen I (Coll I) and, in a more important way, determining a higher production of mineralized matrix nodules.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues

Posa

Benedetto

Colaianni

et al. 2016

Stem Cells International

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“…These findings support an autocrine/paracrine role of vitamin D metabolism in osteoblastogenesis of hMSCs. There are striking age-associated declines in baseline osteoblast differentiation of hMSCs [4–7], as well as in in vitro stimulation of osteoblastogenesis by 1α, 25(OH) 2 D 3 [8], 25(OH)D 3 [4], and PTH (1-34) [9]. The combination of 25(OH)D 3 and PTH-pretreatment, however, rejuvenated osteoblast differentiation in hMSCs from elders [4].…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylation mediates the rejuvenation of osteoblastogenesis by the combination of 25(OH)D3 and parathyroid hormone in MSCs from elders

Zhou

Geng

Glowacki

2013

The Journal of Steroid Biochemistry and Molecular Biology

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Vitamin D metabolites are important effectors of bone and mineral homeostasis. Human bone marrow stromal cells (hMSCs) are targets of 1α,25-dihydroxyvitamin D [1α, 25(OH)2D] action to promote their differentiation to osteoblasts. Osteoblastogenesis is also stimulated by 25-hydroxyvitamin D [25(OH)D], an effect that requires conversion to 1α, 25(OH)2D3 by 25-hydroxyvitamin D3 1α-hydroxylase (CYP27B1). These findings support an autocrine/paracrine role of vitamin D metabolism in osteoblastogenesis of hMSCs. In this study, we assessed whether and by what mechanisms osteoblastogenesis could be rejuvenated with hMSCs from elders. First, knockdown studies with VDR-siRNA showed that both the pro-differentiation and anti-proliferative effects of 1α, 25(OH)2D3 required VDR. Second, 100 nM 25(OH)D3 (p<0.01 vs. control, ANOVA) and 100 nM PTH1-34 (p<0.05) significantly stimulated alkaline phosphatase activity (a measure of osteoblastogenesis), with a synergistic effect when combined (p<0.001). Scriptaid, an inhibitor of histone deacetylase, blocked the effect of 25(OH)D3 and PTH on osteoblastogenesis. Scriptaid alone downregulated VDR in hMSCs. These data demonstrate that histone deacetylation is required for the synergistic effect of 25(OH)D3 and PTH on osteoblastogenesis in hMSCs. Both VDR siRNA and Scriptaid dowregulated VDR mRNA and inhibited osteoblastogenesis. Thus, epigenetic regulation of the VDR may be central to rejuvenating osteoblastogenesis in hMSCs from elders.

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“…Our observations on VDR gene and protein expression lend support to this, particularly in relation to stimulation by 25(OH)D metabolites, with 25(OH)D 3 having a greater effect on the VDR protein. Activated VDR acts as a transcription factor for osteoblast signature genes, and in hBMSCs, active vit D metabolites stimulate the manufacture of bone matrix proteins that include Col1, OCN and OPN, and increase ALP production that promotes mineralisation [7,13,40,41]. Our data in hBMSCs are consistent with such previous findings, with both 25(OH)D metabolites increasing the transcription of col1 , ocn and opn matrix protein genes, as well as that of opn , rankl , and cyp24a1 and cyp27b1 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these and their 1α-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) 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)D2/D3 and 1,25(OH)2D2/D3 suppressed cell number in both human and mouse cells. The suppression was greater with cholecalciferol (D3) metabolites than with those of ergocalciferol (D2). In both cell types, 25(OH)D2 and 25(OH)D3 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)D2 and 25(OH)D3 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)D2/D3 and 1,25(OH)2D2/D3 in hBMSC and 2T3 cells, and the increase was greater with the D3 metabolites at high concentrations. In hBMSCs, mineralisation was also increased by 25(OH)D2/D3 and 1,25(OH)2D2/D3 at high concentrations, with D3 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 D3 metabolites. These findings suggest that there are differences in the effects of 25-hydroxy and 1α,25(OH)2 metabolites of D3 and D2 on human preosteoblasts and mouse osteoblasts, with the D3 metabolites being more potent in suppressing cell number, increasing ALP activity and influencing mineralisation.

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Clinical characteristics influence in vitro action of 1,25-dihydroxyvitamin D3 in human marrow stromal cells

Cited by 53 publications

References 46 publications

Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues

Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues

Histone deacetylation mediates the rejuvenation of osteoblastogenesis by the combination of 25(OH)D3 and parathyroid hormone in MSCs from elders

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

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