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

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

扫码查看
原文链接
  • 万方数据
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.

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

展开 >

Senior Department of Orthopedics,The Fourth Medical Center of Chinese PLA General Hospital,Beijing,China

National Clinical Research Center for Orthopedics,Sports Medicine & Rehabilitation,Beijing,China

The Department of Orthopedic Surgery,Second Affiliated Hospital of Harbin Medical University,Harbin,China

Jiangsu Key Laboratory of Molecular Medicine,Medical School,Nanjing University,Nanjing,China

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

展开 >

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaBeijing Municipal Natural Science Foundation

8200233081972115822027282022YFC25043002022HQ27

2024

10.1038/s41392-024-01976-0

信号转导与靶向治疗(英文)

信号转导与靶向治疗(英文)

CSTPCD
ISSN：
年,卷(期)：2024.9(10)