Metformin exerts a protective effect on articular cartilage in osteoarthritis rats by activating the SIRT1/p53 signaling pathway
10.3969/j.issn.1006-5725.2024.23.005
- VernacularTitle:二甲双胍通过激活SIRT1/p53信号通路对骨关节炎大鼠关节软骨发挥保护作用
- Author:
Xiang JIA
1
;
Tianjie XU
;
Jiaxin FAN
;
Xiaoling GUO
;
Kainan LIU
;
Hui ZHANG
;
Yongsheng WANG
;
Qian WANG
Author Information
1. 华北理工大学基础医学院(河北唐山 063210);河北省慢性疾病基础医学重点实验室(河北唐山 063210)
- Publication Type:Journal Article
- Keywords:
osteoarthritis;
articular cartilage;
apoptosis;
inflammation;
metformin;
SIRT1/p53 signaling pathway
- From:
The Journal of Practical Medicine
2024;40(23):3306-3316
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the underlying mechanism of metformin's protective effect on articular cartilage in rats afflicted with osteoarthritis.Methods Thirty male SD rats were randomly divided into three groups(n=10 per group)to establish a rat model of knee osteoarthritis.The metformin group received metformin via gavage[200 mg/(kg·d)],while the control and model groups received saline as a control.After 4 weeks,morphological staining was used to observe articular cartilage morphology,and immunohistochemical staining,immunofluores-cence staining,and Western blot were employed to detect the expression of factors related to the SIRT1/p53 signaling pathway,inflammation,and apoptosis.Results Compared to the model group,the metformin group exhibited significantly reduced cartilage structural damage,characterized by a smoother cartilage surface,increased chondrocyte population,and enhanced proteoglycan content.Immunohistochemical staining,immunofluorescence staining,and Western blot analysis revealed significantly higher expression levels of SOX9,Aggrecan,Bcl-2,and SIRT1 proteins in the metformin-treated cartilage tissue compared to the model group.Conversely,lower expression levels of IL-6 TNF-α BAX Caspase-9 and p53 proteins were observed in the metformin group compared to the model group.TUNEL staining results demonstrated a significant reduction in apoptotic chondrocytes within the metformin-treated group when compared with the model group.Conclusion Metformin exerts a protective effect on articular cartilage in SD rat models of osteoarthritis by activating the SIRT1/p53 signaling pathway,leading to decreased chondrocyte apoptosis and inhibition of extracellular matrix degradation.
