Jingyu Zhao, Ao Chen, Rong Wang, Dong Qiu, Haiyun Chen, Jiyu Li, Jin'ge Zhang, Tianxiao Wang, Yue Wang, Yujie Lin, Jiawen Zhou, Yifei Du, Hua Yuan, Yongjie Zhang, Dengshun Miao, Yuli Wang, Jianliang Jin
{"title":"Bmi-1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging.","authors":"Jingyu Zhao, Ao Chen, Rong Wang, Dong Qiu, Haiyun Chen, Jiyu Li, Jin'ge Zhang, Tianxiao Wang, Yue Wang, Yujie Lin, Jiawen Zhou, Yifei Du, Hua Yuan, Yongjie Zhang, Dengshun Miao, Yuli Wang, Jianliang Jin","doi":"10.1002/advs.202404518","DOIUrl":null,"url":null,"abstract":"<p><p>With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi-1 co-localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1-driven Bmi-1 knockout in bone-marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1-driven Bmi-1 overexpression showed a contrasting phenotype to Prx1-driven Bmi-1 knockout in BMSCs. Regarding mechanism, Bmi-1-RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313 bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi-1-EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region -1605 to -1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1-driven Bmi-1 overexpression rescued the SOP induced by Prx1-driven Bmi-1 knockout in BMSCs. Thus, Bmi-1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1-driven Bmi-1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/advs.202404518","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi-1 co-localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1-driven Bmi-1 knockout in bone-marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1-driven Bmi-1 overexpression showed a contrasting phenotype to Prx1-driven Bmi-1 knockout in BMSCs. Regarding mechanism, Bmi-1-RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313 bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi-1-EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region -1605 to -1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1-driven Bmi-1 overexpression rescued the SOP induced by Prx1-driven Bmi-1 knockout in BMSCs. Thus, Bmi-1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1-driven Bmi-1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.