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FRI0025 A crucial role for lectin-like oxidized ldl receptor-1 on joint inflammation in ra
  1. M. Ishikawa1,
  2. H. Ito1,
  3. M. Furu1,
  4. K. Murata1,
  5. H. Shibuya1,
  6. H. Yoshitomi1,
  7. S. Matsuda1,
  8. T. Nakmura2,
  9. Department of Orthopaedic Surgery, Kyoto University, Kyoto, Japan
  1. 1orthopaedics, KYOTO UNIVERSITY
  2. 2orthopaedics, Department of Orthopaedic Surgery, National Hospital Organization Kyoto Medical Center, Kyoto, Japan, kyoto, Japan

Abstract

Background Rheumatoid arthritis (RA) is one of the immune-mediated inflammatory diseases. LOX-1 (Lectin-like oxidized low-density lipoprotein receptor 1), one of functional receptors for oxidized LDL (ox-LDL), is expressed in various cells, including endothelial cells and chondrocytes, and its expression is enhanced by oxidative stress, inflammatory cytokines (1). Several studies have reported that the ox-LDL/LOX-1 axis modulates cartilage degradation in RA (2) (3). Although the importance of LOX-1 in RA is apparent, little is known whether LOX-1 is expressed in the RA synovium, which is a major site of systemic inflammation in RA.

Objectives In this study, we investigate the presence of LOX-1 protein in human synovium, and the functional roles of LOX-1 in the pathogenesis of RA.

Methods Synovial tissues samples with RA patients were prepared at the total knee replacement. Ox-LDL was injected into the knee joints of mice with or without of anti-LOX-1 antibody.

Results The ox-LDL and LOX-1 (Figure 1) protein were clearly identified and colocalized in the synovial tissues in RA joints, particularly in the lining layer and around blood vessels. To assess the role of ox-LDL and LOX-1 in the pathogenesis of arthritis in vivo, ox-LDL, native LDL, or PBS were injected into right knee joints for 7 days and evaluated joint inflammation. Hematoxylin-eosin staining revealed that treatment with ox-LDL caused massive synovial hyperplasia, compared with the controls (Figure 2). In contrast, joints pretreated with the anti-LOX-1 antibody significantly inhibited synovial hyperplasia induced by ox-LDL treatment. Immunohistochemistry study showed prominent LOX-1 and MCP-1 expression (Figure 3, 4) in the cartilage and synovium in the ox-LDL-treated group, whereas the control groups hardly displayed any positive staining.

Conclusions These findings clearly demonstrated that ox-LDL/LOX-1 axis induces synovial inflammation. Therefore, blockade of LOX-1 signal would be beneficial for prevention of the synovial inflammation in the inflammatory arthritis, such as RA.

References

  1. Sawarura T, et al. Nature 1997; 386

  2. Nakagawa T, et al. Arthritis Rheum 2002; 46, 2486-94.

  3. Kakimuma T, et al. Arthritis Rheum 2004; 50, 3495-503.

Disclosure of Interest None Declared

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