Abstract
A testosterone deficiency potentially increases osteoarthritis (OA) symptoms, and dietary protein and exercise affect them. However, their efficacy and their interactions are still unclear. We hypothesized that a high-protein diet (HPD) and regular exercise modulated OA symptoms in testosterone-deficient rats, and it was examined in bilateral orchidectomized (ORX) and monoiodoacetate (MIA)-injected rats. The ORX rats were given a 30 energy percent (En%) protein (HPD) or 17.5 En% protein (CD). Both groups had 39 En% fat in the diet. Non-ORX-CD rats (sham-operation of ORX) were given the CD and no exercise (normal control). After an eight-week intervention, all rats had an injection of MIA into the left knee, and the treatments were continued for an additional four weeks. The non-ORX-CD rats showed a significant increase in body weight compared to the ORX rats, but the ORX rats had elevated fat mass. ORX exacerbated the glucose tolerance by lowering the serum insulin concentrations and increasing insulin resistance. ORX exacerbated the OA symptoms more than the non-ORX-CD. The HPD and exercise improved bone mineral density and glucose metabolism without changing serum testosterone concentrations, while only exercise increased the lean body mass and decreased fat mass, lipid peroxide, and inflammation. Exercise, but not HPD, reduced the OA symptoms, the weight distribution in the left leg, and running velocity and provided better relief than the non-ORX-CD rats. Exercise with HPD improved the histology of the knee joint in the left leg. Exercise reduced lipid peroxide contents and TNF-α and IL-1β mRNA expression in the articular cartilage, while exercise with HPD decreased MMP-3 and MMP-13 mRNA expression as much as in the non-ORX-CD group. In conclusion, moderate aerobic exercise with HPD alleviated OA symptoms and articular cartilage degradation in a similar way in the non-ORX rats with OA by alleviating inflammation and oxidative stress.