1. 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
- Author
-
Xinjie Wu, Yanlei Wang, Xiaoyu Fan, Xin Xu, and Wei Sun
- Subjects
Extracorporeal Shockwave Therapy ,Lipopolysaccharides ,Male ,Aging ,Cell Survival ,Nerve Tissue Proteins ,Methylprednisolone ,Random Allocation ,Femur Head Necrosis ,Animals ,Humans ,Glucocorticoids ,Cell Proliferation ,microRNA ,Forkhead Box Protein O1 ,FOXO1 ,osteonecrosis ,Endothelial Cells ,Femur Head ,Cell Biology ,Rats ,MicroRNAs ,HEK293 Cells ,Gene Expression Regulation ,shockwave ,Angiogenesis Inducing Agents ,Research Paper - Abstract
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.
- Published
- 2022