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Effects of heme oxygenase‐1 on bacterial antigen‐induced articular chondrocyte catabolism in vitro
Author(s) -
Mawatari Taro,
Nakamichi Ikuo,
Suenaga Eiji,
Maloney William J.,
Smith Robert L.
Publication year - 2013
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22394
Subject(s) - chondrocyte , hemin , aggrecan , type ii collagen , cartilage , gene expression , chemistry , heme oxygenase , matrix metalloproteinase , microbiology and biotechnology , heme , biology , in vitro , biochemistry , gene , osteoarthritis , medicine , enzyme , alternative medicine , pathology , anatomy , articular cartilage
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. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1943–1949, 2013