Injectable thermosensitive hydrogel delivering resveratrol protects articular cartilage via SIRT1/HIF1α/MMP13 signaling.

Abstract

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of the articular cartilage, synovial inflammation and subchondral bone sclerosis. There is currently no effective drug treatments for late stage OA. METHODS: Here, we prepare injectable resveratrol (Res) thermosensitive hydrogels, detect its microscopic morphology and release in vitro. Then observing its therapeutic effect on C57BL/6 mice in vivo and femoral heads in vitro also used. Characterization of temperature-sensitive resveratrol gel, chondrosynthesis and catabolism genes, morphology of joint and femoral head from mice. Expression of sirtuin1(SIRT1) and hypoxia inducible factor-1α (HIF1α) is also detected in vivo and in vitro. IL-1β is used to imitate an in vitro osteoarthritis model. RESULTS: Res hydrogels show excellent strain, injectability and temperature sensitive properties, and have an apparent protective effect on the OA articular cartilage. P53 and P21 elevated in DMM mice, when HIF1α and matrix metalloproteinase 13 (MMP13) both increased similarly. While Res activates SIRT1 by suppressing HIF1α nucleus-shuttling to promote chondrocytes proliferation and reduce hypertrophy. CONCLUSION: Taken together, injectable resveratrol thermosensitive hydrogel protects the articular cartilage from degradation and reduces the damage to joints caused by mechanical stress via SIRT1/ HIF1α/MMP13 pathway.