Dual inhibition of TNF-α and IL-1β signaling through BIG2 ameliorates osteoarthritis in mouse and primate models.

Dabigatran, identified from an FDA-approved drug library, dual-suppresses TNF-α and IL-1β signaling via BIG2 and ameliorates osteoarthritis in mice and cynomolgus macaques.

• Why it matters: Osteoarthritis involves chronic inflammatory and metabolic disruption, yet single-agent TNF-α or IL-1β targeting has failed in trials, motivating dual-inhibition strategies.
• What they did: The team screened an FDA-approved drug library for effects on chondrocyte TNF-α/IL-1β signaling, then used biochemical copurification with mass spectrometry to find BIG2 as a dabigatran-binding target.
• The result: In mouse and cynomolgus macaque OA models, dabigatran attenuated cartilage degeneration, alleviated pain, and improved joint function by promoting BIG2-dependent TNFR1 release and enhancing BIG2-mediated IL-1R1 degradation via autophagy-lysosome pathways.

AI summary of the abstract · may contain errors · not medical advice · read the paper.