Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/ß-catenin pathway to prevent SONFH.
Food Funct
; 14(2): 946-960, 2023 Jan 23.
Article
en En
| MEDLINE
| ID: mdl-36541285
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/ß-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/ß-catenin pathway, thereby ameliorating SONFH.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Beta Catenina
/
Células Madre Mesenquimatosas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Food Funct
Año:
2023
Tipo del documento:
Article
País de afiliación:
China