QianKun Yang , ZhiYuan Wei , XiaoYu Wei , Jie Zhang , Yong Tang , Xiang Zhou , Pan Liu , Ce Dou , Fei Luo
{"title":"小鼠骨髓间充质干细胞的骨微结构、破骨细胞分布模式、功能和转录组改变的年龄相关性特征。","authors":"QianKun Yang , ZhiYuan Wei , XiaoYu Wei , Jie Zhang , Yong Tang , Xiang Zhou , Pan Liu , Ce Dou , Fei Luo","doi":"10.1016/j.mad.2023.111877","DOIUrl":null,"url":null,"abstract":"<div><p><span>Deteriorated age-related bone loss<span> is the hallmarks of skeletal aging. However, how the aging of bone marrow mesenchymal stem cells (BMSCs) and </span></span>osteoclasts<span><span> are linked to the bone microstructure degeneration is not yet very clear. In this study, the characteristics of age-related bone loss, distribution patterns of osteoclasts, functional and transcriptomic alterations of BMSCs, hub genes responsible for BMSCs senescence, were analyzed. Our study revealed an age-related declined trends in trabecular and cortical bones of femur, tibia and </span>lumbar vertebra<span><span> in mice, which was accompanied by a shift from the trabecular to cortical bones in osteoclasts. Additionally, middle-aged or aged mice exhibited remarkably reduced dynamic bone formation capacities, along with reversed osteogenic-adipogenic differentiation potentials in BMSCs. Finally, transcriptomic analysis indicated that aging-related signaling pathways were significantly activated in BMSCs from aged mice (e.g., </span>cellular senescence<span>, p53 signaling pathway, etc.). Also, weighted correlation network analysis (WGCNA) and venn diagram analysis based on our RNA-Seq data and GSE35956 dataset revealed the critical role of PTPN1 in BMSCs senescence. Targeted inhibition of PTP1B with AAV-Ptpn1-RNAi dramatically postponed age-related bone loss in middle-aged mice. Collectively, our study has uncovered the age-dependent cellular characteristics in BMSCs and osteoclasts underlying progressive bone loss with advancing age.</span></span></span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The age-related characteristics in bone microarchitecture, osteoclast distribution pattern, functional and transcriptomic alterations of BMSCs in mice\",\"authors\":\"QianKun Yang , ZhiYuan Wei , XiaoYu Wei , Jie Zhang , Yong Tang , Xiang Zhou , Pan Liu , Ce Dou , Fei Luo\",\"doi\":\"10.1016/j.mad.2023.111877\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Deteriorated age-related bone loss<span> is the hallmarks of skeletal aging. However, how the aging of bone marrow mesenchymal stem cells (BMSCs) and </span></span>osteoclasts<span><span> are linked to the bone microstructure degeneration is not yet very clear. In this study, the characteristics of age-related bone loss, distribution patterns of osteoclasts, functional and transcriptomic alterations of BMSCs, hub genes responsible for BMSCs senescence, were analyzed. Our study revealed an age-related declined trends in trabecular and cortical bones of femur, tibia and </span>lumbar vertebra<span><span> in mice, which was accompanied by a shift from the trabecular to cortical bones in osteoclasts. Additionally, middle-aged or aged mice exhibited remarkably reduced dynamic bone formation capacities, along with reversed osteogenic-adipogenic differentiation potentials in BMSCs. Finally, transcriptomic analysis indicated that aging-related signaling pathways were significantly activated in BMSCs from aged mice (e.g., </span>cellular senescence<span>, p53 signaling pathway, etc.). Also, weighted correlation network analysis (WGCNA) and venn diagram analysis based on our RNA-Seq data and GSE35956 dataset revealed the critical role of PTPN1 in BMSCs senescence. Targeted inhibition of PTP1B with AAV-Ptpn1-RNAi dramatically postponed age-related bone loss in middle-aged mice. Collectively, our study has uncovered the age-dependent cellular characteristics in BMSCs and osteoclasts underlying progressive bone loss with advancing age.</span></span></span></p></div>\",\"PeriodicalId\":18340,\"journal\":{\"name\":\"Mechanisms of Ageing and Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2023-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mechanisms of Ageing and Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0047637423001033\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mechanisms of Ageing and Development","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0047637423001033","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
The age-related characteristics in bone microarchitecture, osteoclast distribution pattern, functional and transcriptomic alterations of BMSCs in mice
Deteriorated age-related bone loss is the hallmarks of skeletal aging. However, how the aging of bone marrow mesenchymal stem cells (BMSCs) and osteoclasts are linked to the bone microstructure degeneration is not yet very clear. In this study, the characteristics of age-related bone loss, distribution patterns of osteoclasts, functional and transcriptomic alterations of BMSCs, hub genes responsible for BMSCs senescence, were analyzed. Our study revealed an age-related declined trends in trabecular and cortical bones of femur, tibia and lumbar vertebra in mice, which was accompanied by a shift from the trabecular to cortical bones in osteoclasts. Additionally, middle-aged or aged mice exhibited remarkably reduced dynamic bone formation capacities, along with reversed osteogenic-adipogenic differentiation potentials in BMSCs. Finally, transcriptomic analysis indicated that aging-related signaling pathways were significantly activated in BMSCs from aged mice (e.g., cellular senescence, p53 signaling pathway, etc.). Also, weighted correlation network analysis (WGCNA) and venn diagram analysis based on our RNA-Seq data and GSE35956 dataset revealed the critical role of PTPN1 in BMSCs senescence. Targeted inhibition of PTP1B with AAV-Ptpn1-RNAi dramatically postponed age-related bone loss in middle-aged mice. Collectively, our study has uncovered the age-dependent cellular characteristics in BMSCs and osteoclasts underlying progressive bone loss with advancing age.
期刊介绍：
Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms.
Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.
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