The effect of resveratrol on normal and osteoarthritic chondrocyte metabolism

Abstract

Background: Resveratrol is a polyphenolic compound commonly found in the skins of red grapes. Sirtuin 1 (SIRT1) is a human gene that is activated by resveratrol and has been shown to promote longevity and boost mitochondrial metabolism. We examined the effect of resveratrol on normal and osteoarthritic (OA) human chondrocytes. Methods: Normal and OA chondrocytes were incubated with various concentrations of resveratrol (1 μM, 10 μM, 25 μM and 50 μM) and cultured for 24, 48 or 72 hours or for six weeks. Cell proliferation, gene expression, and senescence were evaluated. Results: SIRT1 was significantly upregulated in normal chondrocytes with resveratrol concentrations of 25 μM and 50 μM on both two- (2D) (both p = 0.001) and three-dimensional (3D) cultures (p = 0.008 and 0.001, respectively). It was significantly upregulated in OA chondrocytes treated with 10 μM, 25 μM and 50 μM resveratrol on 2D cultures (p = 0.036, 0.002 and 0.001, respectively) and at 50 μM concentration on 3D cultures (p = 0.001). At 72 hours, the expression of collagen (COL)-10, aggrecan (AGG), and runt-related transcription factor 2 (RUNX2) was significantly greater in both 25 μM (p = 0.011, 0.006 and 0.015, respectively) and 50 μM (p = 0.019, 0.004 and 0.002, respectively) resveratrol-treated normal chondrocyte cultures. In OA chondrocytes, expression of COL10 and RUNX2 was significantly greater in 25 μM (p = 0.004 and 0.024) and 50 μM (p = 0.004 and 0.019) cultures at 72 hours on 3D cultures. Conclusions: At concentrations of 25 μM and/or 50 μM, resveratrol treatment significantly upregulates SIRT1 gene expression in normal and osteoarthritic chondrocytes. Resveratrol induces chondrocytes into a hypertrophic state through upregulation of COL1, COL10, and RUNX2.