Qian Wang, Guoqiang Shao, Xiaoyi Zhao, Heidi H Wong, Kate Chin, Mackenzie Zhao, Audrey Bai, Michelle S Bloom, Zelda Z Love, Constance R Chu, Zhen Cheng, William H Robinson
Joint injury is associated with risk for development of osteoarthritis (OA). Increasing evidence suggests that activation of fibrinolysis is involved in OA pathogenesis. However, the role of the fibrinolytic pathway is not well understood. Here we showed that the fibrinolytic pathway, which includes plasminogen/plasmin, tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA) and the uPA receptor (uPAR), were dysregulated in human OA joints. Pharmacological inhibition of plasmin attenuated OA progression in a destabilization of the medial meniscus (DMM) mouse model, while genetic deficiency of plasmin activator inhibitor (PAI-1), or injection of plasmin, exacerbated OA...
March 19, 2024: JCI Insight