Effects of heme oxygenase-1 on bacterial antigen-induced articular chondrocyte catabolism in vitro
This study tested the hypothesis that heme oxygenase-1 (HO-1) expression counteracts bacterial antigen-induced catabolic metabolism in human articular chondrocytes. HO-1 expression was induced in chondrocytes by the iron-containing porphoryin, hemin. Anti-catabolic and anti-apoptotic effects of HO-1 expression were evaluated following bacterial antigen (lipopolysaccharides, LPS) activation of chondrocytes by quantification of cytokine and cartilage matrix protein expression. Effects of HO-1 over-expression on chondrocyte matrix metabolism were evaluated using plasmid-driven protein synthesis. Hemin increased HO-1 expression and LPS increased interleukin-1beta and interleukin-6 gene and protein expression in chondrocytes. Hemin-induced HO-1 decreased LPS-induced interleukin-1beta and interleukin-6 gene and protein expression. Increased HO-1 expression partially reversed LPS-suppression of aggrecan and type II collagen gene expression and suppressed LPS-induced gene expression of IL-6, inducible nitric oxide synthase (iNOS), matrix metalloproteinases (MMPs), and IL-1beta. HO-1 induction was inversely correlated with LPS-induced chondrocyte apoptosis. HO-1 over-expression in chondrocytes decreased matrix protein gene expression. With LPS activation, increased HO-1 expression decreased chondrocyte catabolism, partially reversed LPS-dependent inhibition of cartilage matrix protein expression and protected against apoptosis. Without LPS, hemin-induced HO-1 and plasmid-based over-expression of HO-1 inhibited cartilage matrix gene expression. The results suggest that elevated HO-1 expression in chondrocytes is protective of cartilage in inflamed joints but may otherwise suppress matrix turn over.