{"title":"淫羊藿苷通过增强绝经后骨质疏松症中SOST甲基化促进骨髓间充质干细胞成骨分化并抑制成脂分化。","authors":"Xu Chen, Xizhe Liu, Junming Wan, Yanqing Hu, Fuxin Wei","doi":"10.1002/jgm.70010","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Purpose</h3>\n \n <p>Postmenopausal osteoporosis (PMO) is mainly concerned with the imbalance of bone resorption and bone formation. Icariin (ICA) plays a vital role in bone protection. This study investigated the mechanism of ICA in PMO rats.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The rats were treated with ovariectomy (OVX) and ICA. Bone structure parameters were measured by Micro-CT. BMSCs were obtained from normal rats, OVX rats, and ICA-treated rats. BMSCs were infected with SOST overexpression lentivirus, and TWS119, an activator of Wnt pathway, was introduced for joint experiment. The binding of ERα to SOST promoter was verified. OVX/ICA rats were injected with DNA methyltransferase inhibitor 5-Aza-dC.</p>\n </section>\n \n <section>\n \n <h3> Result</h3>\n \n <p>ICA increased bone mass and decreased bone marrow fat content in OVX rats. ICA facilitated osteogenic differentiation and repressed adipogenic differentiation of BMSCs. Overexpressing SOST antagonized the effect of ICA, whereas TWS119 rescued the effect of overexpressing SOST. ICA reduced SOST expression by attenuating the effect of ERα. Methylation of SOST inhibited ERα binding to SOST promoter. In vivo experiments confirmed that ICA improved bone mass and reduced bone marrow fat content by enhancing SOST methylation.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Overall, ICA upregulated SOST methylation and inhibited the binding of ERα to SOST promoter, thereby promoting osteogenic differentiation and repressing adipogenic differentiation of BMSCs.</p>\n </section>\n </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 1","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Icariin Facilitates Osteogenic Differentiation and Suppresses Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Enhancing SOST Methylation in Postmenopausal Osteoporosis\",\"authors\":\"Xu Chen, Xizhe Liu, Junming Wan, Yanqing Hu, Fuxin Wei\",\"doi\":\"10.1002/jgm.70010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Purpose</h3>\\n \\n <p>Postmenopausal osteoporosis (PMO) is mainly concerned with the imbalance of bone resorption and bone formation. Icariin (ICA) plays a vital role in bone protection. This study investigated the mechanism of ICA in PMO rats.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The rats were treated with ovariectomy (OVX) and ICA. Bone structure parameters were measured by Micro-CT. BMSCs were obtained from normal rats, OVX rats, and ICA-treated rats. BMSCs were infected with SOST overexpression lentivirus, and TWS119, an activator of Wnt pathway, was introduced for joint experiment. The binding of ERα to SOST promoter was verified. OVX/ICA rats were injected with DNA methyltransferase inhibitor 5-Aza-dC.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Result</h3>\\n \\n <p>ICA increased bone mass and decreased bone marrow fat content in OVX rats. ICA facilitated osteogenic differentiation and repressed adipogenic differentiation of BMSCs. Overexpressing SOST antagonized the effect of ICA, whereas TWS119 rescued the effect of overexpressing SOST. ICA reduced SOST expression by attenuating the effect of ERα. Methylation of SOST inhibited ERα binding to SOST promoter. In vivo experiments confirmed that ICA improved bone mass and reduced bone marrow fat content by enhancing SOST methylation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Overall, ICA upregulated SOST methylation and inhibited the binding of ERα to SOST promoter, thereby promoting osteogenic differentiation and repressing adipogenic differentiation of BMSCs.</p>\\n </section>\\n </div>\",\"PeriodicalId\":56122,\"journal\":{\"name\":\"Journal of Gene Medicine\",\"volume\":\"27 1\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-01-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Gene Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jgm.70010\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gene Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jgm.70010","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Icariin Facilitates Osteogenic Differentiation and Suppresses Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Enhancing SOST Methylation in Postmenopausal Osteoporosis
Purpose
Postmenopausal osteoporosis (PMO) is mainly concerned with the imbalance of bone resorption and bone formation. Icariin (ICA) plays a vital role in bone protection. This study investigated the mechanism of ICA in PMO rats.
Methods
The rats were treated with ovariectomy (OVX) and ICA. Bone structure parameters were measured by Micro-CT. BMSCs were obtained from normal rats, OVX rats, and ICA-treated rats. BMSCs were infected with SOST overexpression lentivirus, and TWS119, an activator of Wnt pathway, was introduced for joint experiment. The binding of ERα to SOST promoter was verified. OVX/ICA rats were injected with DNA methyltransferase inhibitor 5-Aza-dC.
Result
ICA increased bone mass and decreased bone marrow fat content in OVX rats. ICA facilitated osteogenic differentiation and repressed adipogenic differentiation of BMSCs. Overexpressing SOST antagonized the effect of ICA, whereas TWS119 rescued the effect of overexpressing SOST. ICA reduced SOST expression by attenuating the effect of ERα. Methylation of SOST inhibited ERα binding to SOST promoter. In vivo experiments confirmed that ICA improved bone mass and reduced bone marrow fat content by enhancing SOST methylation.
Conclusion
Overall, ICA upregulated SOST methylation and inhibited the binding of ERα to SOST promoter, thereby promoting osteogenic differentiation and repressing adipogenic differentiation of BMSCs.
期刊介绍：
The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies.
Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials.
Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.
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