数字中医药（英文）2019，Vol.2Issue(2)：105-116,12.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
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.关键词
壮骨止痛方/骨质疏松症/SOST/Wnt/LRP5/β-catanin/Runx2/OsxKey words
Zhuang Gu Zhi Tong Formula (ZGZTF)/Osteoporosis/SOST/Wnt/LRP5/β-catenin/Runx2/Osx引用本文复制引用
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].数字中医药（英文）,2019,2(2):105-116,12.基金项目
We thank for the funding support from the National Natural Science Foundation of China (No. 81573956), Natural Science Foundation of Hunan Province (No. 2018JJ2297), Key Program of Chinese Medicine Science Research Plan of Hunan Province (No. 201612), Key Program of Scientific Research Fund of Hunan Provincial Education Department (No. 16A162), National College Students Innovation and Entrepreneurship Project (No. 201710541002) and The Project of Research Learning and Innovative Experiment for College Students in Hunan (No. 2015217, No. 2015220, No. 2016284 and No. 2016281). （No. 81573956）
