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To explore the involvement of protease‐activated receptor 1 (PAR‐1) and PAR‐2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR‐1 or PAR‐2 in mice.

OA was induced in the joints of wild‐type (WT), PAR‐1^+/+, PAR‐1^−/−, and PAR‐2^−/− mice by destabilization of the medial meniscus (DMM), and scores of histologic features (cartilage aggrecan loss and erosion, subchondral bone sclerosis, osteophytes, and synovitis) were compared at 1, 4, and 8 weeks post‐DMM. The effects of PAR ablation on cartilage degradation and chondrocyte metalloproteinase expression/activity were studied in cultures of mouse femoral head tissue with or without interleukin‐1α (IL‐1α). At 1 week post‐DMM, synovial expression of cytokines and metalloproteinase genes was measured by reverse transcription–polymerase chain reaction, and …