Vitamin D endocrine system and osteoclasts.
Vitamin D endocrine system and osteoclasts.
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DOI：
10.1038/bonekey.2013.229
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Suda, Tatsuo
中科院分区：
文献类型：
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作者：
Takahashi, Naoyuki;Udagawa, Nobuyuki;Udagawa, Naoyuki;Suda, Tatsuo
维生素D被发现是一种预防骨矿化失败的抗佝偻病药物，但现在确定维生素D3（1α，25（OH）2D 3）的活性形式诱导骨吸收。核因子-κB配体受体激活剂（RANKL）的发现揭示了1α，25（OH）2D 3刺激骨吸收的分子机制。用1α，25（OH）2D 3处理成骨细胞可刺激RANKL表达，进而诱导破骨细胞生成。然而，活性维生素D化合物如骨化三醇（1α，25（OH）2D 3）、阿法骨化醇（1α（OH）D3）和艾地骨化醇（1α，25-二羟基-2 β-（3-羟基丙氧基）维生素D3）已被用作骨质疏松症的治疗药物，因为它们可增加骨质疏松症患者的骨矿物质密度（BMD）。巧合的是，BMD的增加是由骨吸收的抑制引起的。已经进行了几项研究来阐明活性维生素D化合物在体内抑制骨吸收的机制。我们的研究表明，每天给予小鼠艾地骨化醇既不抑制骨髓中破骨细胞前体的数量，也不抑制体外培养中形成的破骨细胞的数量。艾地骨化醇给药抑制成骨细胞中RANKL的表达。本文综述了活性维生素D化合物对骨吸收的体外和体内影响之间的差异是如何引起的。
Vitamin D was discovered as an anti-rachitic agent preventing a failure in bone mineralization, but it is now established that the active form of vitamin D3 (1α,25(OH)2D3) induces bone resorption. Discovery of the receptor activator of nuclear factor -κB ligand (RANKL) uncovered the molecular mechanism by which 1α,25(OH)2D3 stimulates bone resorption. Treating osteoblastic cells with 1α,25(OH)2D3 stimulates RANKL expression, which in turn induces osteoclastogenesis. Nevertheless, active vitamin D compounds such as calcitriol (1α,25(OH)2D3), alfacalcidol (1α(OH)D3) and eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropoxy) vitamin D3) have been used as therapeutic drugs for osteoporosis, as they increase bone mineral density (BMD) in osteoporotic patients. Paradoxically, the increase in BMD is caused by the suppression of bone resorption. Several studies have been performed to elucidate the mechanism by which active vitamin D compounds suppress bone resorption in vivo. Our study showed that daily administration of eldecalcitol to mice suppressed neither the number of osteoclast precursors in the bone marrow nor the number of osteoclasts formed in ex vivo cultures. Eldecalcitol administration suppressed RANKL expression in osteoblasts. This review discusses how the difference between in vitro and in vivo effects of active vitamin D compounds on bone resorption is induced.