The mechanism of curcumin protecting against IL-1β-induced oxidative stress and inflammation in chondrocytes via the Bmp2/Smad5/Runx2 pathway

A core role of chondrocyte survival/death has been suggested in the pathogenesis of osteoarthritis. We explored the underlying molecular mechanism of curcumin protecting against interleukin-1β (IL-1β)-induced chondrocyte injury via the Bone Morphogenetic Protein 2 (Bmp2)/small mothers against decapentaplegic homolog 5 (SMAD5)/runt-related transcription factor 2 (Runx2) pathway. Chondrocytes ATDC5 in vitro inflammatory model was established by IL-1β induction, and treated with curcumin, or SMAD5 small interfering RNA. Levels of extracellular matrix (ECM) type II collagen (Col-II) and aggrecan, Reactive Oxygen Species (ROS), superoxide dismutase (SOD) and Glutathione Peroxidase (GSH-Px), and cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and IL-6 were determined by immunocytochemistry, kits and ELISA. Apoptosis and necrosis were assessed by Annexin V/PI and TUNEL. Matrix metalloproteinase 13 (MMP13), A disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5), Bmp2/SMAD5/Runx2 expression and SMAD5 phosphorylation levels were determined by qPCR and western blot. IL-1β-treated ATDC5 cells showed decreased Col-II, aggrecan in ECM and SOD and GSH-Px levels, as well as increased Apoptosis and levels of MMP13, ADAMTS5, Bmp2, Runx2, ROS, COX-2, TNF-α and IL-6 and SMAD5 phosphorylation (all p < 0.05), whilst curcumin treatment brought about the opposite trends, suggesting that curcumin inhibited oxidative stress, inflammatory response and Apoptosis, and inactivated the Bmp2/SMAD5/Runx2 pathway in IL-1β-treated chondrocytes. Additionally, SMAD5 silencing also caused suppressed oxidative stress, inflammatory response and Apoptosis in IL-1β-treated chondrocytes. Curcumin reduced IL-1β-induced chondrocyte oxidative stress, inflammation, and Apoptosis, and increased ECM secretion by inactivating the Bmp2/SMAD5/Runx2 pathway, thereby exerting a protective effect on injured chondrocytes.

Apoptosis; Bmp2/Smad5/Runx2 pathway; Chondrocytes; Curcumin; Gene silencing; Inflammation; Osteoarthritis; Oxidative stress.