Iksan526 Rice Callus Extract Induces Dedifferentiation of Rabbit Articular Chondrocytes via ERK1/2 and PI-3K/Akt Pathways

The resveratrol-enriched transgenic rice line Iksan526 (IS526), first developed by the Rural Development Administration of Korea using genetic engineering techniques, shows beneficial health effects in mitigating metabolic syndrome and obesity. However, the effects of IS526 on the differentiation of chondrocytes and the underlying mechanism have not been investigated in detail. In this study, the effects and cellular regulatory mechanisms of IS526 on rabbit articular chondrocytes were examined. Following IS526 callus extract treatment, the expression levels of differentiation-related proteins were detected via western blotting, Alcian blue staining and immune-luorescence staining. IS526 decreased the type II collagen and proteoglycan levels in dose- and time-dependent manners. We further analyzed the effects of IS526 on skeleton genesis in zebrafish larvae using Alcian blue staining, which showed a reduction in cartilage formation along with increased production of matrix metalloproteinase (MMP)-13. IS526 also increased the phosphorylation of ERK1/2 and p38 kinase but inhibited the phosphorylation of Akt. Pharmacological inhibition of MMP-13 blocked the IS526-induced decrease in type II collagen levels. Inhibition of p38 kinase or PI-3K/Akt with SB203580 and LY294002 enhanced the suppression of type II collagen, but the blockage of ERK-1/2 by PD98059 rescued IS526-induced dedifferentiation. These results suggested that IS526 regulates type II collagen and MMP-13 expression via the ERK1/2 and PI-3K/Akt pathways in rabbit articular chondrocytes.