Relative potencies of 1,25-(OH)2D3 and 19-Nor-1,25-(OH)2D2 on inducing differentiation and markers of bone formation in MG-63 cells
Relative potencies of 1,25-(OH)2D3 and 19-Nor-1,25-(OH)2D2 on inducing differentiation and markers of bone formation in MG-63 cells
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DOI：
10.1681/asn.v1271468
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发表时间：
2001-07-01
影响因子：
13.6
通讯作者：
Slatopolsky, EA
中科院分区：
文献类型：
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作者：
Finch, JL;Dusso, AS;Slatopolsky, EA
19-Nor-1，25-（OH）（2）D-2是1，25-（OH）（2）D-3的类似物，用于治疗继发性甲状旁腺功能亢进症，因为它抑制甲状旁腺激素的合成和分泌，降低钙和磷血活性。19-Nor-1，25（OH）（2）D-2在促进骨吸收方面的活性比1，25（OH）（2）D-3低约10倍，这部分解释了该类似物在增加血清钙和磷方面的低效力。由于担心19-去甲-1，25-（OH）（2）D-2在骨形成方面的效力也可能低于1，25-（OH）（2）D-3，因此对两种化合物在成骨细胞上的效力进行了比较。在人成骨细胞样细胞系MG-63中，1，25-（OH）（2）D-3和19-去甲-1，25-（OH）（2）D-2在上调维生素D受体含量和抑制增殖方面具有相似的效力。这两种甾醇引起类似的DNA含量和增殖细胞核抗原蛋白表达的减少。1，95-（OH）（2）D-3和19-nor-1，25-（OH）（2）D-2诱导骨形成标志物骨钙素的时间过程和剂量反应研究显示重叠曲线。还在MG-63细胞中研究了对碱性磷酸酶（ALP）活性的影响，MG-63细胞已用甾醇和转化生长因子-β（该细胞系中1，25-（OH）（2）D-3诱导的ALP活性的增强剂）共同处理。单独的转化生长因子-β没有影响，而1，25-（OH）（2）D-3和19-nor-1，25-（OH）（2）D-2类似地增加ALP活性。这些研究表明，19-nor-1，25-（OH）（2）D-2与1，25-（OH）（2）D-3不仅在诱导维生素D受体含量，骨钙素水平，和碱性磷酸酶的活性，而且在控制成骨细胞的生长。因此，19-nor-1，25-（OH）（2）D-2不太可能对骨重建产生有害影响。
19-Nor-1,25-(OH)(2)D-2, an analog of 1,25-(OH)(2)D-3, is used to treat secondary hyperparathyroidism because it suppresses parathyroid hormone synthesis and secretion with lower calcemic and phosphatemic activities. 19-Nor-1,25(OH)(2)D-2 is approximately 10 times less active than 1,25(OH)(2)D-3 in promoting bone resorption, which accounts in part for the low potency of this analog in increasing serum calcium and phosphorus. Concern that 19-nor-1,25-(OH)(2)D-2 also could be less potent than 1,25-(OH)(2)D-3 on bone formation led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)(2)D-3 and 19-nor-1,25-(OH)(2)D-2 had a similar potency in upregulating vitamin D receptor content and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Time-course and dose-response studies on 1,95-(OH)(2)D-3 and 19-nor-1,25-(OH)(2)D-2 induction of the marker of bone formation, osteocalcin, showed overlapping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and transforming growth factor-beta, an enhancer of 1,25-(OH)(2)D-3-induced ALP activity in this cell line. Transforming growth factor-beta alone had no effect, whereas 1,25-(OH)(2)D-3 and 19-nor-1,25-(OH)(2)D-2 increased ALP activity similarly These studies demonstrate that 19-nor-1,25-(OH)(2)D-2 has the same potency as 1,25-(OH)(2)D-3 not only in inducing vitamin D receptor content, osteocalcin levels, and ALP activity but also in controlling osteoblastic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)(2)D-2 would have deleterious effects on bone remodeling.