The systemic bone protective effects of Gushukang granules in ovariectomized mice by inhibiting osteoclastogenesis and stimulating osteoblastogenesis
The systemic bone protective effects of Gushukang granules in ovariectomized mice by inhibiting osteoclastogenesis and stimulating osteoblastogenesis
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骨疏康颗粒抑制破骨细胞生成、刺激成骨细胞生成对去卵巢小鼠的全身骨保护作用
DOI：
10.1016/j.jphs.2018.01.007
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发表时间：
2018-03-01
影响因子：
3.5
通讯作者：
Zhao, Dongfeng
中科院分区：
文献类型：
--
作者：
Wang, Qiang;Zhao, Yongjian;Zhao, Dongfeng
原发性骨质疏松症（primary osteoporosis，POP）是由骨重建不平衡引起的一种严重的疾病，在全球范围内造成了巨大的经济和社会负担。骨疏康颗粒剂是中医治疗POP的常用方剂之一。本研究旨在通过体内和体外实验阐明GSK在骨重建中的确切作用。我们发现GSK可预防去卵巢小鼠的骨丢失和骨质疏松骨参数的改变以及破骨细胞密度的降低。葛兰素史克抑制骨髓巨噬细胞（BMMs）中核因子-κ B配体（RANKL）受体激活剂激活的破骨细胞生成。在分子水平上，GSK抑制了活化T细胞胞质核因子1（NFATc 1）和c-Fos的表达，这两个主要的破骨细胞生成调节因子。GSK还抑制基质金属蛋白酶9（MMP 9）、组织蛋白酶K（Ctsk）、TRAP和碳酸酐酶II（Car 2）的骨吸收基因表达。同时，GSK刺激骨髓间充质干细胞（MSCs）的成骨细胞分化，并增强Osteirx和Runx 2的表达。GSK还刺激Col-1、骨钙素和碱性磷酸酶（ALP）的表达。我们的研究通过抑制破骨细胞生成和刺激成骨细胞生成确立了GSK的全身性骨保护作用，并为治疗POP的新药开发奠定了基础。（C）2018作者。Elsevier B. V.代表日本药理学会制作和主办。这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Primary osteoporosis (POP), which is caused by unbalanced bone remodeling, leads to significant economic and societal burdens globally. Gushukang (GSK) granule serves as one commonly used prescription for POP in Traditional Chinese Medicine (TCM). The present study aimed to clarify the exact roles of GSK in bone remodeling with in vivo and in vitro assays. Here we showed that GSK prevented bone loss and the alternations of osteoporotic bone parameters as well as the decreased density of osteoclast in ovariectomized (OVX) mice. GSK inhibited receptor activator for nuclear factor-kappa B Ligand (RANKL)-activated osteoclastogenesis in bone marrow macrophages (BMMs). At the molecular levels, GSK inhibited the expression of nuclear factor of activated T cells cytoplasm 1(NFATc1) and c-Fos, two master regulators of osteoclastogenesis. GSK also inhibited bone resorbed genetic expression of matrix metalloproteinase 9 (MMP9), cathepsin K (Ctsk), TRAP and carbonic anhydrase II (Car2). Meanwhile, GSK stimulated osteoblastogenesis from bone primary mesenchymal stem cells (MSCs) and enhanced the expression of Osteirx, and Runx2. GSK also stimulated the expression of Col-1, Osteocalcein and alkaline phosphatase (ALP). Our investigation established the systemic bone protective effects of GSK by suppressing osteoclastogenesis and stimulating osteoblastogenesis and laid bases for new drugs discovery in treating POP. (C) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).