Rheumatology: Metformin alleviates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes

Objective: To investigate the therapeutic effect and mechanism of metformin on knee osteoarthritis (OA) in normal diet (ND) mice and high-fat diet (HFD)-induced obese mice

Methods: Medial meniscal destabilization surgery was performed in ND mice or HFD mice with or without metformin in drinking water

Changes in OA joint structure, synovial macrophage infiltration and polarization, circulation, and local leptin and adiponectin levels were assessed

In vitro, the effects of metformin on chondrocytes and macrophages, and the effects of conditioned media from mouse abdominal fat on the mouse chondrocyte cell line ATDC5 and the mouse macrophage cell line RAW264.

RESULTS: Metformin was protective against OA, characterized by a reduction in OARSI scores after 10 weeks of treatment [2.

Furthermore, the effect was more pronounced in HFD mice than in ND mice

Mechanistically, in addition to reducing chondrocyte apoptosis and matrix-degrading enzyme expression and synovial macrophage infiltration and pro-inflammatory differentiation, metformin also reduced leptin secretion from adipose tissue in HFD mice

Conclusions: Metformin may protect knee OA by reducing chondrocyte apoptosis and catabolism, inhibiting synovial macrophage infiltration and pro-inflammatory polarization

Source:

Li D, Ruan G, Zhang Y, et al.