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.

Highlights

  • Introduction iationsOsteoarthritis (OA) is a degenerative joint disease that occurs mainly in the joints of the knees, hips, and hands

  • Testosterone is involved in suppressing the endoplasmic reticulum (ER) stress mechanism involved in inflammation and cell apoptosis and very-low-density lipoprotein formation and lipid export from the liver [10]. These results suggest that a testosterone deficiency potentially triggers OA by increasing inflammation, endoplasmic reticulum stress, and insulin resistance

  • The body weight gain and food efficiency were much lower in the ORX groups than the non-ORX-control diet (CD) group during eight weeks before the MIA injection into the left knee joint induced OA

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Summary

Introduction

Osteoarthritis (OA) is a degenerative joint disease that occurs mainly in the joints of the knees, hips, and hands. OA is initiated by breaking down the joint articular cartilage and progressively changing the underlying bones [1]. OA causes pain, swelling, reduced flexibility, and stiffness, leading to joint dysfunction and disability. OA is the most prevalent joint disease worldwide. The prevalence of symptomatic OA is approximately 9.6% for men and 18% for women aged over 60 years. It is much higher with high variations in Asian countries—the overall prevalence in Asian countries is 20.5–68.0% [2]

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