刘湘琳, 刘乐平, 何蓉, 张叔琦, 赵子仪, 彭婷, 刘慧萍, 张国民. 壮骨止痛方对骨质疏松症中Wnt/β-catenin信号通路拮抗剂SOST的影响[J]. Digital Chinese Medicine, 2019, 2(2): 105-116. DOI: 10.1016/j.dcmed.2019.09.005
引用本文: 刘湘琳, 刘乐平, 何蓉, 张叔琦, 赵子仪, 彭婷, 刘慧萍, 张国民. 壮骨止痛方对骨质疏松症中Wnt/β-catenin信号通路拮抗剂SOST的影响[J]. Digital Chinese Medicine, 2019, 2(2): 105-116. DOI: 10.1016/j.dcmed.2019.09.005
LIU Xiang-Lin, LIU Le-Ping, HE Rong, ZHANG Shu-Qi, ZHAO Zi-Yi, PENG Ting, LIU Hui-Ping, ZHANG Guo-Min. Effects of Zhuang Gu Zhi Tong Formula on Wnt/β-catenin Osteoporosis Pathway Antagonist SOST in Osteoporosis[J]. Digital Chinese Medicine, 2019, 2(2): 105-116. DOI: 10.1016/j.dcmed.2019.09.005
Citation: LIU Xiang-Lin, LIU Le-Ping, HE Rong, ZHANG Shu-Qi, ZHAO Zi-Yi, PENG Ting, LIU Hui-Ping, ZHANG Guo-Min. Effects of Zhuang Gu Zhi Tong Formula on Wnt/β-catenin Osteoporosis Pathway Antagonist SOST in Osteoporosis[J]. Digital Chinese Medicine, 2019, 2(2): 105-116. DOI: 10.1016/j.dcmed.2019.09.005

壮骨止痛方对骨质疏松症中Wnt/β-catenin信号通路拮抗剂SOST的影响

Effects of Zhuang Gu Zhi Tong Formula on Wnt/β-catenin Osteoporosis Pathway Antagonist SOST in Osteoporosis

  • 摘要:
    目的观察壮骨止痛方(ZGZTF)通过干预Wnt/β-catenin信号通路拮抗剂SOST治疗骨质疏松症的作用。
    方法从GEO数据库中分析发现骨质疏松症患者和正常人的显著差异表达的基因SOST,并通过KEGG分析出SOST为Wnt信号通路的拮抗剂。随后我们研究了壮骨止痛方对Wnt信号通路中SOST的影响,建立8周龄的雌性SD大鼠去势诱导骨质疏松症模型。壮骨止痛方灌胃处理12周后,将大鼠分批处死,测定大鼠血清中碱性磷酸酶(ALP),骨钙素(BGP)和雌二醇(E2)的变化,观察右侧股骨的骨密度和组织形态学,测量腰椎的生物力学,以及SOST的表达量。通过Western blot,RT-PCR和免疫组化分析检测Wnt3a,β-catenin,LRP5,Runx2,Osx及其与Wnt/β-catenin信号通路相关的mRNA的表达。
    结果壮骨止痛方治疗12周可明显降低大鼠血清ALP和BGP水平,增加股骨骨密度,提高椎体生物力学性能,最大负荷和弹性模量。关于组织形态学,我们发现壮骨止痛方治疗12周后,股骨有序排列,骨小梁变薄,股骨无明显骨折。在壮骨止痛方的影响下,参与Wnt/β-catenin信号传导途径的LRP5,β-catenin,Runx2和Osx的表达显著上调,并且该信号途径中SOST的表达下调。
    结论这些结果表明壮骨止痛方可能通过下调SOST蛋白表达促进Wnt/β-catenin信号通路的抗骨质疏松症。

     

    Abstract:
    Objective To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis.
    Methods We analyzed the differential genes of patients with osteoporosis and normal subjects from the GEO database and then found SOST with specific expression. We analyzed SOST as an antagonist of the Wnt signaling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then we studied the effect of ZGZTF on SOST in Wnt signaling pathway. Osteoporosis model was induced by ovariectomy (OVX) in 8-week-old female Sprague–Dawley (SD) rats. After 12 weeks of treatment with ZGZTF by intragastric administration, the rats were put to death in batch. The changes of alkaline phosphatase (ALP), bone gla protein (BGP) and estradiol (E2) in serum were determined, and bone mineral density (BMD) and histomorphology of right femur were observed. Biomechanics of lumbar vertebra were measured, and the expression of SOST, Wnt3a, β-catenin, LRP5, Runx2, Osx and their mRNA involving the canonical Wnt/β-catenin signaling pathway were detected by Western blot, RT-PCR and Immunohistochemical analysis. All data were analyzed by SPSS 22.0.
    Results Twelve weeks of treatment with ZGZTF could significantly decrease the level of ALP and BGP in serum, increase the BMD of femurs, and improve the biomechanical capability of vertebral body in maximum loading and elastic modulus. Concerning histomorphology, we found ordered arrangement of trabeculae, slightly thinning of trabeculae and none obvious slight fractures in femurs after 12 weeks of treatment with ZGZTF. The expression of LRP5, β-catenin, Runx2 and Osx involved in the canonical Wnt/β-catenin signaling pathway was significantly up-regulated in the presence of ZGZTF, and the expression of SOST in this pathway was down-regulated.
    Conclusions These results suggest that ZGZTF may be anti-osteoporosis by down-regulating SOST protein to promote Wnt/β-catenin signaling pathway.

     

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