Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH

Xu, Huihui; Liang, Fang; 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, Lan; He, Bangjian; Tong, Peijian; Jin, Hongting

doi:10.1039/d2fo02337g

Cited by 12 publications

(3 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Long‐term or high‐dose administration of glucocorticoids (GCs) has been identified as a major cause of ONFH (Wang et al, 2018; Weinstein et al, 2017). With the proliferation of coronavirus disease 2019 (COVID‐19) and its variants, GCs are increasingly employed as anti‐inflammatory agents to treat acute patients (Fu et al, 2019; Xu et al, 2023). However, this also greatly increases the incidence of steroid‐induced osteonecrosis of the femoral head (SONFH) and is therefore of particular concern (Yu et al, 2021; Zhang et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

HIF‐1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid‐induced osteonecrosis of the femoral head

Yu,

Jiang,

et al. 2024

Journal Cellular Physiology

View full text Add to dashboard Cite

With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high‐dose GCs leads to a variety of problems, of which steroid‐induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia‐inducible factor 1α (HIF‐1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF‐1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS‐treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co‐treated with MPS and HIF‐1α inhibitor. And the effects observed in HIF‐1α activator‐treated chondrocytes were similar to those induced by MPS. And HIF‐1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF‐1α. Furthermore, HIF‐1α affected glucose metabolism in cartilage by increasing the expression of glycolysis‐related genes. In conclusion, HIF‐1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.

show abstract

Section: Introductionmentioning

confidence: 99%

HIF‐1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid‐induced osteonecrosis of the femoral head

Yu,

Jiang,

et al. 2024

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Steroid-induced osteonecrosis of the femoral head (SONFH) represents a progressive and destructive orthopaedic disorder that is induced by long-term and high-dose administration of glucocorticoids (GCs) (Li et al 2018;Fu et al 2019;Xu et al 2023). Within the collapsed femoral head, there is a notable replacement of bone tissue with adipose tissue, leading to the formation of cystic changes.…”

Section: Introductionmentioning

confidence: 99%

LncRNA-H19 Promotes Adipogenic Differentiation Disorder by Regulating miR-130b-3p/PPARγ Axis in Steroid-induced Osteonecrosis of Femoral Head

Lin,

Yi,

Zhou

et al. 2024

Preprint

View full text Add to dashboard Cite

Steroid-induced osteonecrosis of the femoral head (SONFH) represents a frequent and debilitating orthopedic condition. It is widely believed that the adipogenic/osteogenic differentiation disorder of bone marrow mesenchymal stem cells (BMSCs) contributes to the development of SONFH. However, the regulatory mechanism of long non-coding RNAs (lncRNAs) in the differentiation disorder of BMSCs remains elusive. The expression levels of H19 were detected in both femoral head tissues and BMSCs from patients with SONFH. The role of the lncRNA H19 in SONFH was explored through bioinformatics analysis complemented by relevant validation experiments. Our findings revealed that H19 was significantly up-regulated in SONFH tissues as well as BMSCs. Silencing H19 suppressed BMSC adipogenic differentiation in SONFH and the expression of peroxisome proliferator-activated receptor γ (PPARγ). Furthermore, we found that H19 could interact with miR-130b-3p, and miR-130b-3p could directly inhibit PPARγ expression. In conclusion, this study uncovered that abnormally up-regulated H19 leads to abnormal lipogenic differentiation in SONFH by acting as a sponge for miR-130b-3p and upregulating PPARγ.

show abstract

“…Recent studies suggest that the application of MSCs to enhance bone regeneration in patients with SONFH may be a promising therapeutic strategy [27][28][29]. Epigenetics refers to changing the phenotype of organisms by regulating gene expression without changing genetic material, and this change can be inherited.…”

Section: Introductionmentioning

confidence: 99%

Insight into Steroid-Induced ONFH: The Molecular Mechanism and Function of Epigenetic Modification in Mesenchymal Stem Cells

Huang,

Qing,

Xiao

et al. 2023

Biomolecules

View full text Add to dashboard Cite

Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease, which is one of the common causes of hip pain and dysfunction. ONFH has a very high disability rate, which is associated with a heavy burden to patients, families, and society. The pathogenesis of ONFH is not completely clear. At present, it is believed that it mainly includes coagulation dysfunction, abnormal lipid metabolism, an imbalance of osteogenic/adipogenic differentiation, and poor vascularization repair. The prevention and treatment of ONFH has always been a great challenge for clinical orthopedic surgeons. However, recent studies have emphasized that the use of mesenchymal stem cells (MSCs) to treat steroid-induced ONFH (SONFH) is a promising therapy. This review focuses on the role and molecular mechanism of epigenetic regulation in the progress of MSCs in the treatment of SONFH, and discusses the significance of the latest research in the treatment of SONFH from the perspective of epigenetics.

show abstract

Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH

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.

Cited by 12 publications

References 50 publications

HIF‐1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid‐induced osteonecrosis of the femoral head

HIF‐1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid‐induced osteonecrosis of the femoral head

LncRNA-H19 Promotes Adipogenic Differentiation Disorder by Regulating miR-130b-3p/PPARγ Axis in Steroid-induced Osteonecrosis of Femoral Head

Insight into Steroid-Induced ONFH: The Molecular Mechanism and Function of Epigenetic Modification in Mesenchymal Stem Cells

Contact Info

Product

Resources

About