Dose–response relationship for exercise on severity of experimental osteoarthritis in rats: a pilot study

Abstract Objective To investigate the influence of a calibrated exercise on the progression of structural lesions in an experimental model of osteoarthritis (OA) in the rat, and to explore the effect of exercise on the level of chondrocyte caspase-dependent apoptosis and of Hsp70. Methods The OA model was induced by anterior cruciate ligament transection (ACLT). Rats were placed in 4 experimental groups: operated (ACLT) free moving rats, and 3 exercise groups (slight, moderate and intense) subjected to running training. Rats were killed 14 and 28 days after surgery. Results On D14 histological assessment demonstrated a beneficial influence of a slight and a moderate exercise vs control ACLT group. Hsp70 increased significantly in the moderate group vs controls. On D28, histological lesions strongly decreased in the slight and moderate exercise groups vs ACLT group, while an intense effort abolished this beneficial trend. Interestingly, the concomitant course of apoptotic events (caspase 3-positive cells) and the co-expression of Hsp70 in the various groups varied, when significant, in an inverse manner. In the intense group this overexpression was not noted, as a "burn out" appeared, thus leading to a loss of this protective effect. Conclusion This study shows that a calibrated slight or moderate exercise exerts a beneficial influence on the severity of chondral lesions in ACLT rats. Conversely, a strong effort abolishes this chondroprotective effect. This effect could be related to a reduced level of chondrocyte apoptosis through anti-apoptotic capacities of stress-induced Hsp70 overexpression.