title: Effects of heme oxygenase-1 on bacterial antigen-induced articular chondrocyte catabolism in vitro.
abstract: 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.
authors.affiliation: RR&D Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, 94304; Orthopaedic Research Laboratories, Stanford University School of Medicine, 300 Pasteur Drive, R105, Stanford, California, 94305.
authors.forename: Taro
authors.initials: T
authors.lastname: Mawatari
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nakamichi
authors.forename: Eiji
authors.initials: E
authors.lastname: Suenaga
authors.forename: William J
authors.initials: WJ
authors.lastname: Maloney
authors.forename: Robert L
authors.initials: RL
authors.lastname: Smith
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000166:cytology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D006427:Hemin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: articular chondrocytes; bacterial antigen; cartilage matrix proteins; catabolism; heme oxygenase-1