title: LOX-1 expressed in cultured rat chondrocytes mediates oxidized LDL-induced cell death-possible role of dephosphorylation of Akt.
abstract: The oxidative changes of lipids in cartilage proceed with ageing and with the grade of osteoarthritis. To clarify the role of oxidatively modified lipids in articular cartilage in osteoarthritis, here, we investigated lectin-like oxidized LDL receptor (LOX-1) in rat cultured articular chondrocytes. LOX-1 expression was detectable in basal culture condition and enhanced by the treatment of oxidized LDL and interleukin-1beta. DiI-labeled oxidized LDL was bound and ingested by chondrocytes via LOX-1. Oxidized LDL dose-dependently reduced chondrocyte viability, inducing non-apoptotic cell death, which was again suppressed by anti-LOX-1 antibody treatment. Oxidized LDL reduced the amount of phosphorylated Akt, a substrate of PI3 kinase via LOX-1. Consistently, the PI3 kinase inhibitor, LY294002, decreased cell viability dose-dependently, and the PI3 kinase activator, IGF-I, reversed the effect of oxidized LDL on the cell death. LOX-1 might be involved in the pathogenesis of osteoarthritis, inducing chondrocyte death through PI3 kinase/Akt pathway.
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University Graduates School of Medicine, Kyoto, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Hajime
authors.initials: H
authors.lastname: Hoshikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.forename: Takumi
authors.initials: T
authors.lastname: Kakinuma
authors.forename: Mingyi
authors.initials: M
authors.lastname: Chen
authors.forename: Tomoh
authors.initials: T
authors.lastname: Masaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008055:Lipids; D008077:Lipoproteins, LDL / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000096:biosynthesis*; D051131:Receptors, Oxidized LDL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D007375:Interleukin-1; D008055:Lipids; D008077:Lipoproteins, LDL; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C495136:OLR1 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494920:Akt1 protein, rat