Gushukang inhibits osteocyte apoptosis and enhances BMP-2/Smads signaling pathway in ovariectomized rats
Gushukang inhibits osteocyte apoptosis and enhances BMP-2/Smads signaling pathway in ovariectomized rats
复制标题
骨疏康抑制去卵巢大鼠骨细胞凋亡并增强BMP-2/Smads信号通路
DOI：
10.1016/j.phymed.2019.153063
复制
发表时间：
2019-11-01
期刊：
影响因子：
7.9
通讯作者：
Huang, Hong-Xing
中科院分区：
文献类型：
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作者：
Chai, Shuang;Wan, Lei;Huang, Hong-Xing
工作背景：骨疏康具有促进成骨细胞生成和改善钙稳态的作用，已被临床用于治疗原发性骨质疏松症。目的：本研究旨在探讨GSK对BMP-2/Smsds信号通路及骨细胞凋亡的影响，并探讨GSK对骨细胞凋亡的影响。BMP-2/Smsds信号通路受到抑制，骨细胞凋亡增多。GSK通过上调BMP-2、p-Smad 1和p-Smad 5、Osterix和Runx 2的表达，增强BMP-2/Smsds信号通路，通过上调Bcl-xl和下调巴克的表达，抑制骨细胞凋亡，与ALP、Trap和TUNEL染色显示的组织学变化一致。骨密度、micro-CT测量和HE染色显示GSK治疗能改善OVX大鼠股骨远端骨密度和骨小梁微结构。结论：GSK具有促进骨形成和阻止骨细胞凋亡的保护作用。其机制可能与其对BMP-2/Smads信号通路和Bcl-2家族的调节有关。
Background: Traditional herbal formula Gushukang (GSK) has been clinically applied to treat primary osteoporosis, which can stimulate osteoblastogenesis and improve calcium homeostasis. However, it remains unknown the mechanism that GSK against ovariectomized (OVX) induced damage.Purpose: The aim of this study was to investigate the effect of GSK on BMP-2/Smsds signaling pathway and osteocyte apoptosis which has been reported to play a central role in bone remodeling.Study design: OVX in rat was established and GSK was administered.Results: BMP-2/Smsds signaling pathway was inhibited and the number of apoptotic osteocytes was increased in OVX rats. Treatment with GSK significantly enhanced BMP-2/Smsds signaling pathway by up-regulating the expression of BMP-2, p-Smad1 and p-Smad5, Osterix and Runx2, and inhibited osteocyte apoptosis by up-regulating Bcl-xl and down-regulating Bak, which were consistent with histological changes revealed by ALP, Trap and TUNEL staining. GSK treatment improved bone mass and micro-structure of trabecular bone at distal femur in OVX rats shown by BMD, micro-CT measurement and HE staining.Conclusion: These data suggest that GSK exhibited protective effects on promoting bone formation and precluding osteocyte apoptosis. The underlying mechanism may be attributed to its regulation on BMP-2/Smads signaling pathway and Bcl2 family.