Effect of β‑ecdysterone on glucocorticoid‑induced apoptosis and autophagy in osteoblasts

Abstract

The aim of the present study was to investigate the effect of glucocorticoids in osteoblasts and to examine the role of β-ecdysterone in the pathogenesis of glucocorticoid-induced osteoporosis. Osteoblasts were induced from bone marrow mesenchymal stem cells, which were isolated from C57BL/6 mice. Cell viability and apoptosis of osteoblasts were measured by Cell Counting Kit-8 and flow cytometry analysis, respectively. The expression of related genes and proteins was measured by reverse transcription quantitative polymerase chain reaction and western blot analysis respectively. Dose-dependent decreases in the cell proliferation and differentiation were observed in dexamethasone (Dex)-treated osteoblasts, evidenced by downregulation in the activity of alkaline phosphatasedecreased expression levels of Runt-related transcription factor 2 and osteocalcin, and upregulated expression of RANK ligand. Dex also induced apoptosis and inhibited autophagy of osteoblasts, evidenced by upregulated B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 ratio and the activation of mammalian target of rapamycin (mTOR), and decreased expression levels of Beclin-1, autophagy protein 5 and microtubule-associated protein 1 light chain 3 II. The effects on cell proliferation, apoptosis and autophagy induced by Dex were reversed by β-ecdysterone in a dose-dependent manner. Therefore, β-ecdysterone may be a promising candidate drug for the treatment of osteoporosis through inducing osteoblast autophagic activity by inactivating mTOR.

β‑ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration

“…β-ecdysterone treatment induces autophagy in nucleus pulposus cells. A previous study indicated that β-ecdysterone inhibited cell apoptosis by induction of autophagy in osteoblasts (20). To determine whether β-ecdysterone has a role in autophagy in nucleus pulposus cells, cells were treated with different concentrations of β-ecdysterone or for different time intervals in the present study.…”

“…β-ecdysterone has been demonstrated to exhibit a number of functions, including anabolic and hepatoprotective effects (20). Certain studies have indicated that β-ecdysterone may increase the synthesis of collagen protein and inhibit cell apoptosis by regulation of autophagy (20)(21)(22). However, the roles of β-ecdysterone on nucleus pulposus cells and IDD remain incompletely characterized.…”

The Effects of Biomaterial Implant Wear Debris on Osteoblasts

“…Numerous studies suggest that autophagy modulates osteoblastic function (Kaluderović et al, 2014;Nollet et al, 2014;Wang et al, 2015b;Kim et al, 2016;Kang et al, 2017;Tang et al, 2018). Also, autophagy has been reported to be triggered by wear particles in osteoblasts (Wang et al, 2015b).…”

Osthole improves therapy for osteoporosis through increasing autophagy of mesenchymal stem cells

“…In vitro study proposed that upregulated autophagy could protect osteoblast cells from tumor necrosis-α-induced [50] and oxidative stress-mediated apoptosis [19]. Induction of osteoblast autophagic activity by β-ecdysterone inactivating mTOR is reported to be the mechanism for treating glucocorticoid-induced osteoporosis [40]. So in our study, the exact molecular targets for osthole to induce autophagy activity and the mechanisms for osthole-induced autophagy to promote osteoblast differnentiation of BMMSCs still needs and is worthy of further investigations.…”