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调节骨代谢的新分子——骨质疏松症治疗的新视角

New molecules modulating bone metabolism - new perspectives in the treatment of osteoporosis.

作者信息

Zofkova I, Blahos J

机构信息

Institute of Endocrinology, Prague, Czech Republic, Osteocentrum, Central Military Hospital, Prague, Czech Republic.

出版信息

Physiol Res. 2017 Sep 26;66(Suppl 3):S341-S347. doi: 10.33549/physiolres.933720.

Abstract

In this review the authors outline traditional antiresorptive pharmaceuticals, such as bisphosphonates, monoclonal antibodies against RANKL, SERMs, as well as a drug with an anabolic effect on the skeleton, parathormone. However, there is also a focus on non-traditional strategies used in therapy for osteolytic diseases. The newest antiosteoporotic pharmaceuticals increase osteoblast differentiation via BMP signaling (harmine), or stimulate osteogenic differentiation of mesenchymal stem cells through Wnt/beta-catenin (icarrin, isoflavonoid caviunin, or sulfasalazine). A certain promise in the treatment of osteoporosis is shown by molecules targeting non-coding microRNAs (which are critical for osteoclastogenesis) or those stimulating osteoblast activity via epigenetic mechanisms. Vitamin D metabolites have specific antiosteoporotic potencies, modulating the skeleton not only via mineralization, but markedly also through the direct effects on the bone microstructure.

摘要

在这篇综述中,作者概述了传统的抗吸收药物,如双膦酸盐、抗核因子κB受体活化因子配体(RANKL)单克隆抗体、选择性雌激素受体调节剂(SERM),以及一种对骨骼具有合成代谢作用的药物甲状旁腺激素。然而,文中也重点介绍了溶骨性疾病治疗中使用的非传统策略。最新的抗骨质疏松药物通过骨形态发生蛋白(BMP)信号通路增加成骨细胞分化(哈尔明),或通过Wnt/β-连环蛋白刺激间充质干细胞的成骨分化(淫羊藿素、异黄酮卡维宁或柳氮磺胺吡啶)。靶向非编码微小RNA(对破骨细胞生成至关重要)的分子或通过表观遗传机制刺激成骨细胞活性的分子在骨质疏松症治疗中显示出一定的前景。维生素D代谢物具有特定的抗骨质疏松效力,不仅通过矿化作用调节骨骼,而且对骨微结构也有显著的直接影响。

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