RRC ID 52045
Author Funato S, Yasuhara R, Yoshimura K, Miyamoto Y, Kaneko K, Suzawa T, Chikazu D, Mishima K, Baba K, Kamijo R.
Title Extracellular matrix loss in chondrocytes after exposure to interleukin-1β in NADPH oxidase-dependent manner.
Journal Cell Tissue Res
Abstract Osteoarthritis is a degenerative joint disease caused by excessive death of chondrocytes and loss of the extracellular matrix (ECM) in articular cartilage. We previously reported that reactive oxygen species (ROS) generated by the NADPH oxidase (NOX) isoform NOX-2 are involved in chondrocyte death induced by interleukin-1β (IL-1β). In this study, we investigate the role of NOX-2 in the production and degradation of ECM by chondrocytes. Although IL-1β lowered the mRNA expression of type II collagen (Col2a1) and aggrecan (Acan) in mouse chondrocyte-like ATDC5 cells, RNA silencing of Nox2 did not change the mRNA expression of these major components of the ECM of cartilage. Hence, NOX-2 is not involved in the IL-1β-induced suppression of ECM production. On the other hand, the NOX inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), the ROS scavenger N-acetylcysteine and an antisense oligodeoxynucleotide for Nox2 prevented the loss of proteoglycan induced by IL-1β in highly differentiated ATDC5 cells. Furthermore, AEBSF did not affect the expression of hyaluronidase-1 and -2, whereas it suppressed hyaluronidase activity in culture medium. IL-1β-induced intra- and extracellular acidification was also suppressed by AEBSF, as was the antisense oligodeoxynucleotide for Nox2. Since hyaluronidase activity is known to be higher under acidic conditions, NOX-2 probably contributes to ECM loss by the activation of hyaluronidase through acidification.
Volume 368(1)
Pages 135-144
Published 2017-4-1
DOI 10.1007/s00441-016-2551-2
PII 10.1007/s00441-016-2551-2
PMID 28070636
MeSH Acetylcysteine / pharmacology Acids / metabolism Aggrecans / genetics Aggrecans / metabolism Cells, Cultured Chondrocytes / drug effects Chondrocytes / metabolism* Collagen Type II / genetics Collagen Type II / metabolism Culture Media / pharmacology Enzyme Inhibitors / pharmacology Extracellular Matrix / drug effects Extracellular Matrix / metabolism* Gene Expression Regulation / drug effects Humans Hyaluronic Acid / metabolism Hyaluronoglucosaminidase / metabolism Hydrogen-Ion Concentration Interleukin-1beta / pharmacology* NADPH Oxidases / metabolism* Proteoglycans / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Sulfones / pharmacology
IF 4.044
Times Cited 8
Human and Animal Cells ATDC5(RCB0565)