Histologically, no changes in articular cartilage was found in rat knee joints forced to run 15 km. MIA injection did clearly induced a loss of sulphated-glycosaminoglycans (sGAG) in both femoral and tibial cartilages (Fig. 4a). On the tibial side, cartilage degeneration induced by MIA was observed around the apex part of the tibia, which was not covered with the meniscus. Though the forced running did not affect the femoral cartilage, the forced running further exacerbated the sGAG loss of the cartilage affected by MIA in the tibial cartilage (Fig. 4b). OARSI score for histology was significantly higher in the MIA-treated groups than in the MIA untreated groups both in the femoral and tibial cartilages (Fig. 4b). Interestingly, in the tibial cartilage, OARSI score was significantly higher in the running group than in the non-running group in the MIA-treated condition. This difference was attributed not to stage (area volume) but to grade (tissue reaction); in the MIA treated non-running group, the tibial grade was 2 (cartilage matrix depletion into upper 1/3) or 3 (cartilage matrix depletion into lower 2/3), while in the MIA treated running group, the tibial grades had risen to 3 or 4 (cartilage matrix loss).Fig. 4Histological observation for articular cartilage. a Femoral and tibial sections stained with safranin-o in the sagittal plane. b OARSI scores for femoral and tibial cartilage (n =4, * p < 0.05 by Steel-Dwass test)