The Protective Effect of Luteolin in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.

Jingdi Zhan,Yijiang Huang,Weihui Qi,Xiaoyun Pan,Zijian Yan,Xinghe Xue,Jian Lin

doi:10.3389/fphar.2020.01195

Abstract

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a frequently occurring type of nontraumatic osteonecrosis. A failure of the timely treatment can eventually result in the collapse of the subchondral bone structure. Luteolin (Lut), a compound extracted from Rhizoma Drynariae, is reported to possess multiple pharmacological properties including anticancer, antioxidant, antiapoptosis, and antiinflammatory properties. However, whether Lut has a protective effect on the development of GIONFH remains unclear. In this study, we evaluated the effect of Lut on Dexamethasone (Dex)-induced STAT1/caspase3 pathway in vitro and evaluated GIONFH model in vivo. In vitro, Lut inhibited the upregulation of Dex-induced phospho-STAT1, cleaved caspase9, and cleaved caspase3. In addition, Lut inhibited Dex-induced expression of Bax and cytochrome c and increased the expression of B cell lymphoma-2(Bcl-2). In vivo, Lut decreased the proportion of empty lacunae in rats with GIONFH. Taken together, these findings indicate that Lut may have therapeutic potential in the treatment of GIONFH. Further, this effect might be achieved by suppressing mitochondrial apoptosis of osteoblasts via inhibition of STAT1 activity.

Highlights

Osteonecrosis of the femoral head (ONFH) is a progressive orthopedic disease, including traumatic and nontraumatic osteonecrosis (Nazal et al, 2019)
enzyme linked immunosorbent assay (ELISA) further confirmed that Lut had a protective effect on apoptosis induced by Dex (Figure 1E)
A higher proportion of C-caspase3-positive cells were observed in the model group, and Lut could attenuate the abovementioned effect induced by Dex (Figure 7)

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is a progressive orthopedic disease, including traumatic and nontraumatic osteonecrosis (Nazal et al, 2019). Glucocorticoid-induced ONFH (GIONFH) is a frequently occurring type of nontraumatic osteonecrosis, which can eventually result in the collapse of the subchondral bone structure if not treated timely (Kerachian et al, 2009; Deng et al, 2019). It is increasingly evident that the effects of glucocorticoids on normal bone metabolism may be the main cause of GIONFH (Kuang et al, 2019). Osteoblasts, as the main target of glucocorticoids, play important roles in the Effect of Luteolin in GIONFH process of bone formation; further, dexamethasone (Dex) has been reported to induce apoptosis of mouse osteoblasts (Brennan-Speranza et al, 2012; Gamez et al, 2016; Gu et al, 2019)

Methods

Results

Conclusion