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.
Highlights
Osteonecrosis is regarded as bone cell death initiated by an impairment of the blood supply to the bone [1]
We demonstrated that Extracorporeal shockwave treatment (ESWT) promotes endothelial cells (ECs) proliferation, migration, and www.aging-us.com www.aging-us.com angiogenesis as well as attenuates apoptosis in vitro and in vivo
MiR-135b downregulation blocked the beneficial effects of ESWT on proliferation, migration, angiogenesis, and antiapoptosis in both human umbilical vein ECs (HUVECs) and bone microvascular ECs (BMECs)
Summary
Osteonecrosis is regarded as bone cell death initiated by an impairment of the blood supply to the bone [1]. While the exact pathogenesis and molecular mechanisms that contribute to ONFH remain indefinite, it seems that endothelial cells (ECs) injury and dysfunction play a crucial role in the course of the disease. Extracorporeal shockwave treatment (ESWT) has been proven to be able to enhance angiogenesis via stimulating localized stress on the membranes of ECs, which is similar to fluid shear stress in blood vessels [4, 5]. A comprehensive assessment of the www.aging-us.com effects of ESWT and miRNAs on steroid-induced ONFH has still not been reported. We explored the potential role of ESWT in the proliferation, apoptosis, migration, and angiogenesis of ECs. In addition, we attempted to obtain insight into the molecular and signaling mechanisms of effects of ESWT on ONFH
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