Exploring the therapeutic applications of metformin in articular cartilage repair: mechanistic insights and translational perspectives
Abstract
Articular cartilage is characterized by an avascular structure and limited intrinsic regenerative capacity. The most prevalent pathological conditions that lead to cartilage damage are osteoarthritis (OA) and rheumatoid arthritis (RA). In recent decades, cartilage homeostasis has been shown to be particularly vulnerable to metabolic disturbances, especially those induced by obesity and diabetes mellitus. Metformin, a first-line antidiabetic agent and emerging antiaging therapeutic, has garnered significant attention as a promising candidate for cartilage repair that can address the unmet clinical need for treating currently irreversible cartilage damage and associated pathologies such as OA and RA. This review synthesizes preclinical and clinical evidence to elucidate the multifaceted effects of metformin on cartilage homeostasis. Cellular and animal studies have demonstrated that metformin exerts chondroprotective effects through multiple complementary mechanisms, including the activation of AMPK/SIRT1-mediated autophagy, the suppression of NF-κB signaling, the inhibition of matrix-degrading enzymes, the reduction of oxidative stress and inflammatory mediators, the modulation of macrophage polarization toward an anti-inflammatory phenotype, and the attenuation of aberrant subchondral bone remodeling. Emerging clinical evidence suggests that metformin may attenuate OA progression and ameliorate clinical symptoms. However, further large-scale, prospective trials are warranted…
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.