The distal femur, proximal tibia and whole knee joints were fixed in 4% paraformaldehyde for 7 days, decalcified in 20% EDTA solution for 21 days, and then embedded in paraffin wax. The specimens were sectioned in the sagittal plane at 5 μm and stained with safranin-o/fast green. Each section was evaluated with the Osteoarthritis Research Society International histological grading system (OARSI score: 0 to 24) for articular cartilage degeneration . For evaluation of synovium, 7 days after MIA injections, before and after 15 km of running, whole knee joints were sectioned in a sagittal plane and stained with hematoxylin-eosin (HE). Each section was evaluated with Krenn’s synovitis grading system (Synovitis score: 0 to 9) for infrapatellar fat pad (IFP) synovitis . Histologic sections were visualized using an Olympus BX53 microscope (Olympus, Tokyo, Japan). Microscopic assessment was performed separately by two examiners and the average values were recorded.