Inhibition of complement C3 prevents osteoarthritis progression in guinea pigs by blocking STAT1 activation

• DOI: 10.1038/s42003-024-06051-6
• Publication Date: 2024-03-27T18:05:09Z
• Authors: Jen X. Xu; Frank Z. Xu; Amelia Furbish; Alicia M. Braxton; Brook Brumfield; Kristi L. Helke; Yuri K. Peterson
• Keywords: Pathogenesis; STAT1; Mediator

Abstract Osteoarthritis (OA) is one of the leading causes disability, affecting over 500 million adults worldwide. Previous studies have found that various inflammatory factors can contribute to pathogenesis OA, including complement in synovial fluid OA patients. However, this disease still not known, and only therapy severe total joint replacements. Total replacements are invasive, expensive, affect quality life. Here we show when human articular chondrocytes stimulated with pro-inflammatory mediator interleukin-1β (IL-1β) there an increase component 3 (C3). We also transcription factor, signal transducer activator 1 (STAT1), responsible for increased C3 expression after IL-1β stimulation chondrocytes. A specific STAT1 inhibitor, fludarabine, attenuates hyper-expression delays/prevents spontaneous Dunkin-Hartley guinea pigs. Since fludarabine already clinically used chemotherapy, study has great translational potential as a unique disease-modifying osteoarthritis drug (DMOAD) treating primary OA.