title: Oxidative stress-induced apoptosis and matrix loss of chondrocytes is inhibited by eicosapentaenoic acid.
abstract: Eicosapentaenoic acid (EPA) is an antioxidant and n-3 polyunsaturated fatty acid that reduces the production of inflammatory cytokines. We evaluated the role of EPA in chondrocyte apoptosis and degeneration. Normal human chondrocytes were treated with EPA and sodium nitroprusside (SNP). Expression of metalloproteinases (MMPs) was detected by real-time polymerase chain reaction (PCR) and that of apoptosis-related proteins was detected by western blotting. Chondrocyte apoptosis was detected by flow cytometry. C57BL/6J mice were used for the detection of MMP expression by immunohistochemistry and for investigation of chondrocyte apoptosis. EPA inhibited SNP-induced chondrocyte apoptosis, caspase 3 and poly(ADP-ribose) polymerase cleavage, phosphorylation of p38 MAPK and p53, and expression of MMP3 and MMP13. Intra-articular injection of EPA prevented the progression of osteoarthritis (OA) by inhibiting MMP13 expression and chondrocyte apoptosis. EPA treatment can control oxidative stress-induced OA progression, and thus may be a new approach for OA therapy.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Sakata
authors.forename: Shinya
authors.initials: S
authors.lastname: Hayashi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Fujishiro
authors.forename: Kohei
authors.initials: K
authors.lastname: Kawakita
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kanzaki
authors.forename: Shingo
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Iwasa
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Chinzei
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kihara
authors.forename: Masahiko
authors.initials: M
authors.lastname: Haneda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueha
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009599:Nitroprusside / Q000494:pharmacology; D010003:Osteoarthritis / Q000188:drug therapy; D018384:Oxidative Stress; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D009599:Nitroprusside; D015118:Eicosapentaenoic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053509:Matrix Metalloproteinase 13
keywords: chondrocyte; eicosapentaenoic acid; matrix metalloproteinase; osteoarthritis