ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis and inhibits bone resorption after bone marrow ablation
ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis and inhibits bone resorption after bone marrow ablation
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DOI：
10.1016/j.bone.2006.08.017
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发表时间：
2007-02-01
期刊：
影响因子：
4.1
通讯作者：
Asou, Y.
中科院分区：
文献类型：
--
作者：
Okuda, N.;Takeda, S.;Asou, Y.
艾德-71是1 α，25-（OH）（2）D-3的一种新型类似物，与1 α，25-（OH）（2）D-3前药阿法骨化醇相比，其增加骨量的程度更大。在这项研究中，我们使用了小鼠骨髓消融模型来比较艾德-71与1 α，25-（OH）（2）D-3对体内骨形成和骨吸收的影响。我们发现，骨髓消融后第一周内发生的骨基质重塑被单次注射艾德-71增强，但不被1 α，25-（OH）（2）D-3增强。这种增强与骨表面的增加有关。单次注射艾德-71可抑制术后1 - 2周发生的小梁骨吸收，但注射1 α，25-（OH）（2）D-3则不能，尽管成骨细胞表面增加，但治疗小鼠破骨细胞数量减少。如单次注射所见，每日施用艾德-71也增强骨建模。艾德-71预处理也增强了骨髓成骨细胞的分化。此外，骨髓消融后立即给予艾德-71治疗通过增强VEGF（120）表达增强了骨髓腔内的血管生成。在本文中，我们清楚地表明，艾德-71是一种口服给药的小分子量化合物，对骨代谢的合成代谢作用。(c)2006爱思唯尔公司All rights reserved.
ED-71, a novel analog of 1 alpha,25-(OH)(2) D-3, increases bone mass to a greater extent than alfacalcidol, an 1 alpha,25-(OH)(2) D-3 prodrug. In this study, we used a murine bone marrow ablation model to compare the effect of ED-71 on bone formation and resorption in vivo with that of 1 alpha,25-(OH)(2) D-3. We discovered that bone matrix remodeling occurring within the first week after bone marrow ablation was enhanced by a single injection of ED-71, but not by 1 alpha,25-(OH)(2) D-3. This enhancement was associated with an increase in bone surface. Trabecular bone resorption occurring from 1 to 2 weeks after the procedure was suppressed by a single injection of ED-71, but not 1 alpha,25-(OH)(2) D-3, with treated mice exhibiting a reduction in osteoclast numbers, despite increases in osteoblast surface. As seen with the single injection, daily administration of ED-71 also enhanced bone modeling. Bone marrow osteoblast differentiation was also augmented by ED-71 pretreatment. Furthermore, ED-71 treatment immediately after bone marrow ablation enhanced angiogenesis within the bone marrow cavity via enhancement of VEGF(120) expression. In this paper, we clearly demonstrate that ED-71 is an orally administered small molecular weight compound with an anabolic effect on bone metabolism. (c) 2006 Elsevier Inc. All rights reserved.