The Influence of Vitamin D Metabolism on Gene Expression, Matrix Production and Mineralization During Osteoprecursor Cell-Based Bone Development.
The Influence of Vitamin D Metabolism on Gene Expression, Matrix Production and Mineralization During Osteoprecursor Cell-Based Bone Development.
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维生素D代谢对基于整骨细胞骨发育过程中基因表达，基质产生和矿化的影响。
DOI：
10.14740/jem212w
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发表时间：
2014-04
影响因子：
0.4
通讯作者：
Zelick RD
中科院分区：
文献类型：
--
作者：
Mason SS;Kohles SS;Winn SR;Zelick RD
来源于人骨髓的多能前体细胞系能够分化为软骨或骨，可能为研究组织再生所需的生长和分化因子的调节和代谢提供有用的组织发育模型。在哺乳动物中，骨发育过程依赖于成骨细胞谱系细胞的增殖和分化，以及随后骨细胞外基质（ECM）的合成和矿化。维生素D代谢物在骨骼和矿物质平衡中起着关键作用，是骨骼发育的积极因素。最近，研究表明，来源于人骨髓的人源性工程成骨前体细胞（OPC1）可以将母体前体维生素D3 （vitaD3）代谢为活性类固醇1α，25-二羟基维生素D3 (1,250 oh2d3)，并引发成骨反应，导致早期骨发育过程中增殖减少和ECM合成增加。本研究的目的是在骨发育模型中表征基因表达、基质生产和矿化。我们研究了在OPC1s的融合培养中，vitaD3是否以与1,250 oh2d3相同的方式影响骨ECM矿化。此外，我们还探讨了维生素D代谢物联合抗坏血酸、β-甘油磷酸酯、地塞米松（dex）和重组人骨形态发生蛋白-2 （rhBMP-2）等常用成骨因子对OPC1成骨的影响。结果表明，OPC1表达了将维生素ad3转化为1,250 oh2d3所需的酶促设备的mRNA，以及已知调节活性1,250 oh2d3浓度的分解代谢酶的mRNA表达。研究还表明，维生素D受体（VDR）的mRNA表达同时受到维生素ad3和1,250 oh2d3的影响。维生素D代谢物与抗坏血酸、β-甘油磷酸酯、dex和/或rhBMP-2联合使用对碱性磷酸酶（ALP）活性、钙沉积、I型前胶原（proColI）、骨钙素（OC）和骨桥蛋白（OP） mRNA表达的影响存在差异。综上所述，维生素D联合成骨因子对颞骨发育顺序有积极的影响。
Multipotential precursor cell lines derived from human bone marrow, capable of differentiating into cartilage or bone, may provide a useful tissue development model for studying the regulation and metabolism of putative growth and differentiation factors necessary for tissue regeneration. In mammals, the process of bone development depends on the proliferation and differentiation of osteoblast lineage cells, and the subsequent synthesis and mineralization of bone extracellular matrix (ECM). Vitamin D metabolites play a pivotal role in bone and mineral homeostasis, and are positive factors on bone development. Recently, it was demonstrated that a human-derived engineered osteoblast precursor cell line (OPC1), derived from human bone marrow, can metabolize the parental precursor vitamin D3 (vitaD3) to the active steroid 1α,25-dihydroxyvitamin D3 (1,25OH2D3), and elicit an osteogenic response that results in the decrease in proliferation and increase in ECM synthesis during early bone development. The aim in this study is to characterize gene expression, matrix production and mineralization within a bone development model. We investigated whether vitaD3 influences bone ECM mineralization in the same manner as 1,25OH2D3 in confluent cultures of OPC1s. In addition, we explored the influence of vitamin D metabolites, in combination with other commonly used osteogenic factors, ascorbic acid, β-glycerophosphate, dexamethasone (dex) and recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteoinduction of OPC1. It was demonstrated that OPC1 expresses the mRNA for the enzymatic equipment necessary to convert vitaD3 to 1,25OH2D3, as well as the mRNA expression of the catabolic enzyme known to regulate the concentration of active 1,25OH2D3. It was also demonstrated that mRNA expression for the vitamin D receptor (VDR) was influenced by both vitaD3 and 1,25OH2D3. Differential results using vitamin D metabolites in combination with ascorbic acid, β-glycerophosphate, dex and/or rhBMP-2 were observed in alkaline phosphatase (ALP) activity and calcium deposition, and mRNA expression of procollagen type I (proColI), osteocalcin (OC) and osteopontin (OP). Overall it was demonstrated that vitamin D in combination with osteogenic factors influences the temporal bone development sequence in a positive manner.