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LOX-1 deficient mice show resistance to zymosan-induced arthritis

Kazuhiko Hashimoto, Yutaka Oda, Koichi Nakagawa, Terumasa Ikeda, Kazuhiro Ohtani, Masao Akagi
  • Yutaka Oda
    Kindai University Hospital, Japan
  • Koichi Nakagawa
    Kindai University Hospital, Japan
  • Terumasa Ikeda
    Kindai University Hospital, Japan
  • Kazuhiro Ohtani
    Kindai University Hospital, Japan
  • Masao Akagi
    Kindai University Hospital, Japan

Abstract

Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX-1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KOmice with ZIA or the saline-injected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.

Keywords

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1); oxidized low-density lipoprotein (ox-LDL); Arthritis

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Submitted: 2017-09-02 03:19:54
Published: 2018-01-22 15:16:04
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Copyright (c) 2018 Kazuhiko Hashimoto, Yutaka Oda, Koichi Nakagawa, Terumasa Ikeda, Kazuhiro Ohtani, Masao Akagi

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