Resveratrol inhibits the development of obesity-related osteoarthritis via the TLR4 and PI3K/Akt signaling pathways

ABSTRACT

Aim of the study: Obesity leads to mild, chronic inflammation which is a primary risk factor for osteoarthritis (OA). Resveratrol exerts a protective effect on OA through its anti-inflammatory properties, but the precise mechanism remains unknown. The present study aimed to investigate the mechanism by which resveratrol alleviates obesity-related OA, and whether it is linked to the TLR4 and PI3K/Akt signaling pathways.

Materials and methods: C57BL/6J male mice were fed a high-fat diet (HFD) with or without resveratrol treatment and knee joints were collected for analysis. In addition, IL-1β-induced SW1353 cells were used to study in vitro the reciprocal effects of TLR4 and PI3K/Akt pathways.

Results: Resveratrol inhibited the development of OA in mice fed a HFD. TLR4 and PI3K/Akt signaling pathways were both activated in the articular cartilage; resveratrol treatment down-regulated TLR4 but up-regulated PI3K/Akt signaling. Further in vitro results showed that the effect of resveratrol alone on activation of PI3K/Akt was attenuated but not abolished by the TLR4 inhibitor CLI-095, and resveratrol failed to reduce TLR4 protein expression in IL-1β stimulated cells pretreated with the PI3K inhibitor LY294002.

Conclusions: Resveratrol may exert an anti-osteoarthritic effect by inhibiting TLR4 via the activation of PI3K/Akt signaling pathways. Resveratrol has potential as a drug for OA prevention.

KEYWORDS:

• Osteoarthritis
• toll-like receptor 4
• PI3K/Akt signaling pathway
• resveratrol
• high-fat diet

Disclosure statement

The authors declare that they have no conflicts of interest with the contents of this article.

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (No. 81372971) and Shenyang Science and Technology Project (No. RC170476).