期刊
AGING-US
卷 14, 期 1, 页码 410-429出版社
IMPACT JOURNALS LLC
关键词
shockwave; osteonecrosis; micro RNA; FOXO1
资金
- National Natural Science Foundation of China [82072524, 81871830]
- Natural Science Foundation of Beijing Municipality [7182146]
- Fundamental Research Funds for the Central Universities and Research Projects on Biomedical Transformation of the China-Japan Friendship Hospital [PYBZ1828]
- Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Center
The present study reveals that ESWT alleviates endothelial injury and dysfunction in steroid-induced ONFH by targeting FOXO1 through miR-135b, promoting proliferation, angiogenesis, and reducing apoptosis.
Injury and dysfunction of endothelial cells (ECs) are closely related to the pathogenesis of steroid-induced osteonecrosis of the femoral head (ONFH), while MicroRNAs (miRNAs) play an essential role in the processes. Extracorporeal shockwave treatment (ESWT) has been used in the non-invasive treatment of various diseases including musculoskeletal and vascular disorders. In particular, ESWT with low energy levels showed a beneficial effect in ischemic tissues. However, there has been no comprehensive assessment of the effect of ESWT and miRNAs on steroid-induced ONFH. In the present study, we investigated the role and mechanism of ESWT and miRNAs both in vitro and in vivo. Using a steroid-induced ONFH rat model, we found that ESWT significantly enhances proliferation and angiogenesis as well as alleviates apoptosis. In two types of ECs, ESWT can promote cell proliferation and migration, enhance angiogenesis, and inhibit apoptosis. Notably, our study demonstrates that miR-135b is downregulated and modulated forkhead box protein O1 (FOXO1) in ECs treated with dexamethasone. Remarkably, both miR-135b knockdown and FOXO1 overexpression reversed the beneficial effect of ESWT on ECs. Additionally, our data suggest that ESWT activates the FOXO1-related pathway to impact proliferation, apoptosis, and angiogenesis. Taken together, this study indicates that ESWT relieves endothelial injury and dysfunction in steroid-induced ONFH via miR-135b targeting FOXO1.
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