Eldecalcitol, a second-generation vitamin D analog, drives bone minimodeling and reduces osteoclastic number in trabecular bone of ovariectomized rats
Eldecalcitol, a second-generation vitamin D analog, drives bone minimodeling and reduces osteoclastic number in trabecular bone of ovariectomized rats
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DOI：
10.1016/j.bone.2011.05.022
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发表时间：
2011-09-01
期刊：
影响因子：
4.1
通讯作者：
Amizuka, Norio
中科院分区：
文献类型：
--
作者：
Luiz de Freitas, Paulo Henrique;Hasegawa, Tomoka;Amizuka, Norio
为了阐明艾地骨化醇（目前正在等待批准作为治疗骨质疏松症的药物的第二代维生素D类似物）给药后的组织学事件，我们采用了卵巢切除术（OVX）大鼠模型。OVX大鼠接受溶媒或30 ng/kg艾地骨化醇，假手术动物仅接受溶媒。12周后处死大鼠，取出股骨和胫骨，进行组织化学和组织形态计量学分析。与OVX组相比，艾地骨化醇治疗组大鼠的骨细胞数量和骨吸收参数显著减少，同时伴有骨形成参数降低。前成骨细胞层，与骨细胞前体相互作用，相互分化，在艾地骨化醇组中发育不良，表明前成骨细胞和破骨细胞前体之间的细胞与细胞接触较少。有趣的是，艾地骨化醇确实促进了一种不依赖于骨吸收的局灶性骨形成，这一过程被称为骨微型模型。骨髓中艾德-1阳性巨噬细胞数量增加，但骨细胞数量减少。总之，我们的研究结果表明，艾地骨化醇刺激前成骨细胞分化，而不是他们的增殖，这反过来可能会阻止或减少前成骨细胞和骨细胞前体之间的细胞与细胞接触，因此，导致破骨细胞数量减少，骨吸收减少。(C)2011 Elsevier Inc. All rights reserved.
To elucidate the histological events that follow administration of eldecalcitol, a second-generation of vitamin D analog currently awaiting approval as a drug for treatment of osteoporosis, we employed the ovariectomy (OVX) rat model. OVX rats received vehicle or 30 ng/kg of eldecalcitol, and sham-operated animals received vehicle only. Rats were sacrificed after 12 weeks and had their femora and tibiae removed and processed for histochemical and histomorphometrical analyses. When compared with OVX group, osteoclastic number and bone resorption parameters were significantly reduced in eldecalcitol-treated rats, accompanied by decreased bone formation parameters. The preosteoblastic layer, with which osteoclastic precursors interact for mutual differentiation, was poorly developed in the eldecalcitol group, indicating less cell-to-cell contact between preosteoblasts and osteoclast precursors. Interestingly, eldecalcitol did promote a type of focal bone formation that is independent of bone resorption, a process known as bone minimodeling. While the number of ED-1-positive macrophages was higher in the bone marrow of treated rats, though osteoclastic number was deceased. Taken together, our findings suggest that eldecalcitol stimulates preosteoblastic differentiation rather than their proliferation, which in turn may prevent or diminish cell-to-cell contact between preosteoblasts and osteoclastic precursors, and therefore, lead to lower osteoclast numbers and decreased bone resorption. (C) 2011 Elsevier Inc. All rights reserved.