EPCR blocking prevents the degeneration of cartilage and elaboration of IL-6 in the synovium of FVIII^−/− mice following hemarthrosis. FVIII^−/− mice were administered with EPCR-blocking mAb (bl. EPCR mAb), EPCR-nonblocking mAb (non-bl. EPCR mAb), or no mAb (No tr.). Twenty-four hours later, joint bleeding was induced with a needle puncture (I). UN indicates an uninjured knee. (A) Two weeks after the injury, mice were killed, knee joints were excised, and joint tissue sections were stained with Safranin O/Fast Green Staining. Top panel images were captured at 4 magnification. The squared area was imaged at ×40 magnification (bottom panel). Arrows point out the articular cartilage. Loss of red stain in the articular cartilage region indicates the loss of glycosaminoglycans in the region and cartilage degeneration. (B) The quantified score of cartilage degeneration based on Safranin O/Fast Green Staining (0-3 scale; 0, normal/bright red staining of cartilage; 1, a slight reduction in staining; 2, a moderate reduction in staining; and 3, severe reduction/complete loss of staining). (C) One week after the injury, mice were killed, and synovial fluids were collected. IL-6 levels in synovial fluids were measured in enzyme-linked immunosorbent assay. The data shown are mean ± SEM (n = 4-7 mice/group). ***P < .001