Repurposing metformin for treating osteoarthritis via leveraging Nrf2 signaling
Abstract
There are currently no satisfactory effective treatments for osteoarthritis (OA), the most common degenerative joint disease leading to progressive disability in the elderly population. The effects of metformin, a first-line medication for type 2 diabetes, on OA and its underlying mechanisms remain obscure. Through a systematic review, we identified that oxidative stress played a significant role in the pathogenesis of OA, and metformin had potential antioxidative capacity in relieving various chronic inflammation-related diseases, raising the possibility of treating OA. Firstly, we observed that metformin was able to partially alleviate OA pain in the monosodium iodoacetate (MIA)-induced mouse model as assessed by animal behavior tests. Moreover, micro-CT and histological analysis demonstrated that metformin could moderately delay the progression of OA as well. Further in vitro and in vivo experiments uncovered metformin's ability to suppress oxidative stress by promoting the expression of Nuclear factor erythroid 2-related factor 2 (Nrf2). The deficiency of Nrf2 in Nrf2 knockout (KO) mice attenuated the chondroprotective effect of metformin on OA development, further affirming the core position of Nrf2 signaling during metformin fights illness as an antioxidant. Retrospective analysis of OA progress in type 2 diabetes patients showed the lower ratio of knee arthroplasty in patients treated with metformin, suggesting the possibility of clinical effectiveness. In conclusion,…
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.