Zijun Chen, Yuxi Wang, Guanhua Zhang, Jian Zheng, Lei Tian, Yingliang Song, Xiangdong Liu
{"title":"LRP5/6/GSK-3β/β-catenin在艾塞那肽和胰岛素促进的T2D成骨和骨调节差异中的作用","authors":"Zijun Chen, Yuxi Wang, Guanhua Zhang, Jian Zheng, Lei Tian, Yingliang Song, Xiangdong Liu","doi":"10.1111/bph.16421","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Purpose</h3>\n \n <p>Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D.</p>\n </section>\n \n <section>\n \n <h3> Experimental Approach</h3>\n \n <p>In vivo, micro-CT was used to detect differences in the peri-implant bone microstructure in vivo. Histology, dual-fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT-PCR and western blotting were used to measure the expression of osteogenesis- and Wnt signalling-related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT-PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation.</p>\n </section>\n \n <section>\n \n <h3> Key Results</h3>\n \n <p>Micro-CT and section staining showed exenatide extensively promoted peri-implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis-related and activated the LRP5/6/GSK-3β/β-catenin-related Wnt pathway. Furthermore, exenatide suppressed expression of <i>Bmpr1a</i> to inhibit lipogenesis and promoted expression of <i>Btrc</i> to suppress inflammation.</p>\n </section>\n \n <section>\n \n <h3> Conclusion and Implications</h3>\n \n <p>Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. In addition to its dependence on LRP5/6/GSK-3β/β-catenin signalling for osteogenic differentiation, exenatide-mediated osteomodulation also involves inhibition of inflammation and adipogenesis by BMPR1A and β-TrCP, respectively.</p>\n </section>\n </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of LRP5/6/GSK-3β/β-catenin in the differences in exenatide- and insulin-promoted T2D osteogenesis and osteomodulation\",\"authors\":\"Zijun Chen, Yuxi Wang, Guanhua Zhang, Jian Zheng, Lei Tian, Yingliang Song, Xiangdong Liu\",\"doi\":\"10.1111/bph.16421\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background and Purpose</h3>\\n \\n <p>Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Experimental Approach</h3>\\n \\n <p>In vivo, micro-CT was used to detect differences in the peri-implant bone microstructure in vivo. Histology, dual-fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT-PCR and western blotting were used to measure the expression of osteogenesis- and Wnt signalling-related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT-PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Key Results</h3>\\n \\n <p>Micro-CT and section staining showed exenatide extensively promoted peri-implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis-related and activated the LRP5/6/GSK-3β/β-catenin-related Wnt pathway. Furthermore, exenatide suppressed expression of <i>Bmpr1a</i> to inhibit lipogenesis and promoted expression of <i>Btrc</i> to suppress inflammation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion and Implications</h3>\\n \\n <p>Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. 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Role of LRP5/6/GSK-3β/β-catenin in the differences in exenatide- and insulin-promoted T2D osteogenesis and osteomodulation
Background and Purpose
Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D.
Experimental Approach
In vivo, micro-CT was used to detect differences in the peri-implant bone microstructure in vivo. Histology, dual-fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT-PCR and western blotting were used to measure the expression of osteogenesis- and Wnt signalling-related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT-PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation.
Key Results
Micro-CT and section staining showed exenatide extensively promoted peri-implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis-related and activated the LRP5/6/GSK-3β/β-catenin-related Wnt pathway. Furthermore, exenatide suppressed expression of Bmpr1a to inhibit lipogenesis and promoted expression of Btrc to suppress inflammation.
Conclusion and Implications
Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. In addition to its dependence on LRP5/6/GSK-3β/β-catenin signalling for osteogenic differentiation, exenatide-mediated osteomodulation also involves inhibition of inflammation and adipogenesis by BMPR1A and β-TrCP, respectively.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.