The Journal of Practical Medicine ›› 2024, Vol. 40 ›› Issue (23): 3306-3316.doi: 10.3969/j.issn.1006-5725.2024.23.005

• Basic Research • Previous Articles    

Metformin exerts a protective effect on articular cartilage in osteoarthritis rats by activating the SIRT1/p53 signaling pathway

Xiang JIA1,2,Tianjie XU1,2,Jiaxin FAN1,2,Xiaoling GUO1,2,Kainan LIU3,Hui ZHANG4,Yongsheng WANG1,2,Qian. WANG1,2()   

  1. *.School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063210,Hebei,China
    *.Key Laboratory of Basic Medicine for Chronic Diseases,Tangshan 063210,Hebei,China
  • Received:2024-08-23 Online:2024-12-10 Published:2024-12-16
  • Contact: Qian. WANG E-mail:tswqxx008@126.com

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, immunofluorescence 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.

Key words: osteoarthritis, articular cartilage, apoptosis, inflammation, metformin, SIRT1/p53 signaling pathway

CLC Number: