Research Paper Volume 14, Issue 1 pp 410—429
Extracorporeal shockwave relieves endothelial injury and dysfunction in steroid-induced osteonecrosis of the femoral head via miR-135b targeting FOXO1: in vitro and in vivo studies
- 1 Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
- 2 Department of Orthopedic Surgery, China-Japan Friendship Hospital, Beijing 100029, China
- 3 Beijing University of Chinese Medicine, Beijing 100029, China
- 4 Graduate School of Peking Union Medical College, Beijing 100730, China
Received: September 27, 2021 Accepted: December 29, 2021 Published: January 7, 2022https://doi.org/10.18632/aging.203816
How to Cite
Copyright: © 2022 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.