Abstract

Obesity has been associated with osteoarthritis (OA) due to increased mass and metabolic factors which are independent of the biomechanical contribution to joint load. Resveratrol, a natural polyphenolic compound, exerts protective effects on OA through its anti-inflammatory property. However, the mechanism of resveratrol on obesity-related OA is unclear. To investigate the effect and possible mechanism of oral resveratrol on obesity-related OA, we fed C57BL/6J mice with a high-fat diet (HFD) for 16 weeks to establish obesity-related OA model; then two doses (22.5 mg/kg and 45 mg/kg) of resveratrol were given by gavage for additional 12 weeks. Mice with HFD significantly increased body weights compared to the control mice, while resveratrol treatment did not cause obvious weight loss. Histological assessments showed that resveratrol at 45 mg/kg significantly improved OA symptoms. Levels of serum IL-1β and leptin were decreased by resveratrol treatment and positively correlated with Mankin scores. Moreover, resveratrol significantly inhibited the expression of TLR4 and TRAF6 in cartilage. These results suggest that HFD induced obesity can lead to the occurrence of OA, and resveratrol may alleviate OA pathology by decreasing the levels of systematic inflammation and/or inhibiting TLR4 signaling pathway in cartilage. Thus, resveratrol might be a promising therapeutic treatment for obesity-related OA.

Highlights

  • Osteoarthritis (OA) is the most common chronic joint disease which is due to degenerative changes of the joint

  • Sections stained at week 16 showed that the cartilage thickness was reduced, the arrangement of chondrocyte was disordered, and the cartilage structure exhibited mild damage in high-fat diet (HFD) group (Figure 2(a)). These results demonstrated the successful establishment of HFD induced knee joint OA model

  • Results of Pearson correlation coefficients showed that body weight, serum IL-1β, and leptin, but not adiponectin, were significantly associated with Mankin scores

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Summary

Introduction

Osteoarthritis (OA) is the most common chronic joint disease which is due to degenerative changes of the joint. It is generally regarded as a major cause of disability in elderly population. The pathogenesis of OA is not fully established, obesity is considered as one of the strongest factors of OA development [1]. Weight gain changes the joint load and damages the joints, but the inflammatory and metabolic characteristics of the obesity affect the health of the joints [3]. Obesity is associated with low-grade systemic inflammation [6] and metabolic factors that link obesity and OA. Figuring out the mechanism of obesity-related OA is necessary for the treatment of metabolic OA therapy

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