Taken together, these findings may reveal a promotive role of TLR4 in regulating hyperglycaemia-induced catabolism and inflammation in T2DM-associated OA, and also implicate that TLR4 inhibition might be of therapeutic significance in treating T2DM-associated OA.
Immunohistochemistry, immunoblotting, and immunocytochemistry were performed to identify HMGB1 and its receptors, receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4) in OA knee tissue, chondrocytes, and CPCs.
THP-1 macrophages were cultured with a range of sizes and concentrations of HA fragments with TLR4 (LPS in a physiologically relevant concentration determined by analyses of sera of a community clinic ascertained knee osteoarthritis (OA) cohort) or TLR2 (heat killed listeria bacteria) agonists and varying concentrations of CS in a physiologically relevant range (10-200 μg/ml).