Histone deacetylase inhibition enhances extracellular vesicles from muscle to promote osteogenesis via miR-873-3p  

作　　者：Ming Chen Yi Li Mingming Zhang Siliang Ge Taojin Feng Ruijing Chen Junmin Shen Ran Li Zhongqi Wang Yong Xie Duanyang Wang Jiang Liu Yuan Lin Feifan Chang Junyu Chen Xinyu Sun Dongliang Cheng Xiang Huang Fanfeng Wu Qinxiang Zhang Pingqiang Cai Pengbin Yin Licheng Zhang Peifu Tang 

机构地区：[1]Senior Department of Orthopedics,The Fourth Medical Center of Chinese PLA General Hospital,Beijing,China [2]National Clinical Research Center for Orthopedics,Sports Medicine&Rehabilitation,Beijing,China [3]The Department of Orthopedic Surgery,Second Affiliated Hospital of Harbin Medical University,Harbin,China [4]Jiangsu Key Laboratory of Molecular Medicine,Medical School,Nanjing University,Nanjing,China [5]Innovative Centre for Flexible Devices(iFLEX),Max Planck-NTU Joint Lab for Artificial Senses,School of Materials Science and Engineering,Nanyang Technological University,Singapore,Singapore

出　　处：《Signal Transduction and Targeted Therapy》2024年第10期4730-4748,共19页信号转导与靶向治疗（英文）

基　　金：National Natural Science Foundation of China(82002330,81972115,82202728);National Key Research and Development Program of China(2022YFC2504300);Beijing Municipal Natural Science Foundation(2022HQ27).

摘　　要：Regular physical activity is widely recognized for reducing the risk of various disorders,with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues.However,many individuals,particularly the elderly and those with clinical conditions,are unable to engage in physical exercise,necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules.Histone acetylation and deacetylation significantly influence exercise-induced gene expression,suggesting that targeting histone deacetylases(HDACs)could mimic some exercise responses.In this study,we explored the effects of the HDAC inhibitor Trichostatin A(TSA)on human skeletal muscle myoblasts(HSMMs).Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles(EVs)enriched with miR-873-3p.These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells(hBMSCs)by targeting H2 calponin(CNN2).In vivo,systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass.Moreover,TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs,suggesting that HDAC inhibition can replicate exercise-induced bone health benefits.These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis,particularly for individuals unable to exercise.Given the FDA-approved status of various HDAC inhibitors,this approach holds significant promise for rapid clinical translation in osteoporosis treatment.

关 键 词：ORGANS holds MUSCLE 

分 类 号：R68[医药卫生—骨科学]