Oral Administration of Resveratrol Alleviates Osteoarthritis Pathology in C57BL/6J Mice Model Induced by a High-Fat Diet

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.

The role of leptin in osteoarthritis

“…[ 65 ] Recent findings suggest that high-fat diet (HFD)-induced obesity can lead to the development of OA, whereas resveratrol may relieve OA pathology by reducing systemic inflammation and/or inhibiting TLR4 signaling in cartilage. [ 66 ] Therefore, resveratrol may be a promising treatment for obesity-related OA. For dietary structure, dietary fatty acid content plays an important role in the pathogenesis of OA after joint injury and supports the need for further study of dietary fatty acid supplements as a potential treatment for OA.…”

Efficacy and safety of co-administration of resveratrol with meloxicam in patients with knee osteoarthritis: a pilot interventional study

“…In this regard, resveratrol has demonstrated a great potential in preventing and/or slowing the breakdown of articular cartilage and extracellular matrix in the preclinical studies. 15 In human articular chondrocytes, resveratrol also offers anti-apoptotic, anti-inflammatory, and antioxidant effects. 16 , 27 Similarly, another preclinical study demonstrated the potent anabolic and anti-catabolic potential of resveratrol in human adult articular chondrocytes via the inhibition of the matrix-degrading enzyme.…”

“… 10 – 14 Preclinical studies provided accumulating evidence on its efficacy in ameliorating the degenerative articular damage that mostly attributed to its pleiotropic properties. 15 , 16 Moreover, many pieces of evidence have displayed resveratrol as one of the nutraceutical candidates for OA therapy in human. 17 , 18 Early reports showed that resveratrol has anti-inflammatory activity in acute and chronic phases of inflammation and that the effect was associated with its ability to modulate cyclooxygenase COX-1 and COX-2.…”

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

“…Similar results were observed in obesity-related OA in an animal model. The overall outcomes of this 2017 study indicate that high-fat diet-induced obesity could trigger the onset of OA, and resveratrol might alleviate OA pathology by decreasing systematic inflammation and/or inhibiting the TLR4 signaling pathway in cartilage, posing as a potential therapeutic approach for obesity-related OA [114]. Limagne E. et al investigated the pro-inflammatory paracrine interactions between human primary chondrocytes and macrophages following IL-1β treatment.…”