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维生素D代谢物在体外调节人骨细胞的骨钙素合成和增殖。

Vitamin D metabolites regulate osteocalcin synthesis and proliferation of human bone cells in vitro.

作者信息

Skjødt H, Gallagher J A, Beresford J N, Couch M, Poser J W, Russell R G

出版信息

J Endocrinol. 1985 Jun;105(3):391-6. doi: 10.1677/joe.0.1050391.

DOI:10.1677/joe.0.1050391
PMID:3873510
Abstract

The effects of six natural vitamin D metabolites of potential biological and therapeutic interest, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), 25-hydroxyvitamin D3 (25-OH-D3), 24R,25-dihydroxyvitamin D3 (24R,25-(OH)2D3), 1,24R,25-trihydroxyvitamin D3 (1,24R,25-(OH)3D3), 25S,26-dihydroxyvitamin D3 (25S,26-(OH)2D3) and 1,25S,26-trihydroxyvitamin D3 (1,25S,26-(OH)3D3) on cell replication and expression of the osteoblastic phenotype in terms of osteocalcin production were examined in cultured human bone cells. At a dose of 5 X 10(-12) mol/1, 1,25-(OH)2D3 stimulated cell proliferation, whereas at higher doses (5 X 10(-9)-5 X 10(-6) mol/1) cell growth was inhibited in a dose-dependent manner. The same pattern of effects was seen for the other metabolites in a rank order of potency: 1,25-(OH)2D3 greater than 1,25S,26-(OH)3D3 = 1,24R,25-(OH)3D3 greater than 25S,26-(OH)2D3 = 24R,25-(OH)2D3 = 25-OH-D3. Synthesis of osteocalcin was induced by 1,25-(OH)2D3 in doses similar to those required to inhibit cell proliferation. Biphasic responses were observed for some of the metabolites in terms of osteocalcin synthesis, inhibitory effects becoming apparent at 5 X 10(-6) mol/1. The cells did not secrete osteocalcin spontaneously. These results indicate that vitamin D metabolites may regulate growth and expression of differentiated functions of normal human osteoblasts.

摘要

研究了六种具有潜在生物学和治疗意义的天然维生素D代谢物，即1,25 - 二羟基维生素D3（1,25-(OH)2D3）、25 - 羟基维生素D3（25-OH-D3）、24R,25 - 二羟基维生素D3（24R,25-(OH)2D3）、1,24R,25 - 三羟基维生素D3（1,24R,25-(OH)3D3）、25S,26 - 二羟基维生素D3（25S,26-(OH)2D3）和1,25S,26 - 三羟基维生素D3（1,25S,26-(OH)3D3）对培养的人骨细胞中细胞复制和成骨细胞表型表达（以骨钙素产生衡量）的影响。在5×10(-12) mol/1的剂量下，1,25-(OH)2D3刺激细胞增殖，而在更高剂量（5×10(-9)-5×10(-6) mol/1）时，细胞生长以剂量依赖性方式受到抑制。其他代谢物也呈现相同的效应模式，效力顺序为：1,25-(OH)2D3＞1,25S,26-(OH)3D3 = 1,24R,25-(OH)3D3＞25S,26-(OH)2D3 = 24R,25-(OH)2D3 = 25-OH-D3。1,25-(OH)2D3以与抑制细胞增殖所需剂量相似的剂量诱导骨钙素的合成。就骨钙素合成而言，一些代谢物观察到双相反应，在5×10(-6) mol/1时抑制作用变得明显。细胞不会自发分泌骨钙素。这些结果表明维生素D代谢物可能调节正常人成骨细胞的生长和分化功能的表达。

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