Metformin exerts a protective effect on articular cartilage in osteoarthritis rats by activating the SIRT1/p53 signaling pathway
JIA Xiang
XU Tianjie
FAN Jiaxin
GUO Xiaoling
LIU Kainan
ZHANG Hui
WANG Yongsheng
WANG Qian
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.
Keywords：osteoarthritisarticular cartilageapoptosisinflammationmetforminSIRT1/p53 signaling pathway
Publication Date：2024-12-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：11( 3306-3316 )