Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH. Issue 2 (21st December 2022)

• Record Type: Journal Article
• Authors: Xu, Huihui; Fang, Liang; Zeng, Qinghe; Chen, Jiali; Ling, Houfu; Xia, Hanting; Ge, Qinwen; Wu, Congzi; Zou, Kaiao; Wang, Xu; Wang, Pinger; Yuan, Wenhua; Dong, Rui; Hu, Songfeng; Xiao, Luwei; He, Bangjian; Tong, Peijian; Jin, Hongting
• Is Part Of: Food & function. Volume 14:Issue 2(2023)
• Page Start: 946
• Page End: 960
• Publication Date: 2022-12-21
• Subjects: Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Nutrition -- Periodicals; 664.07
• DOI: 10.1039/d2fo02337g
• Languages: English
• ISSNs: 2042-6496

Abstract

Abstract : GA can reduce the level of OS induced by excessive GCs through the activation of the Wnt/β-catenin signaling pathway, thereby maintaining the osteolipogenic homeostasis of MSCs. Abstract : This study aimed to examine the in vivo and in vitro therapeutic effects of glycyrrhizic acid (GA) on steroid-induced osteonecrosis of the femoral head (SONFH), which is caused by the overuse of glucocorticoids (GCs). Clinically, we identified elevated oxidative stress (OS) levels and an imbalance in osteolipogenic homeostasis in SONFH patients compared to femoral neck fracture (FNF) patients. In vivo, we established experimental SONFH in rats via lipopolysaccharides (LPSs) combined with methylprednisolone (MPS). We showed that GA and Wnt agonist-S8320 alleviated SONFH, as evidenced by the reduced microstructural and histopathological alterations in the subchondral bone of the femoral head and the decreased levels of OS in rat models. In vitro, GA reduced dexamethasone (Dex)-induced excessive NOX4 and OS levels by activating the Wnt/β-catenin pathway, thereby promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibiting lipogenic differentiation. In addition, GA regulated the expression levels of the key transcription factors downstream of this pathway, Runx2 and PPARγ, thus maintaining osteolipogenic homeostasis. In summary, we demonstrated for the first time that GA modulates the osteolipogenic differentiation commitment of MSCs induced by excessive OS through activating the Wnt/β-catenin pathway, thereby ameliorating SONFH.