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OP0210 Apolipoprotein E Aggravates Inflammation and Joint Destruction in Murine Antigen-Induced Arthritis
  1. G. Ascone,
  2. I. Di Ceglie,
  3. W. de Munter,
  4. B. Walgreen,
  5. A. Sloetjes,
  6. P. van Lent,
  7. P. van der Kraan
  1. Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands

Abstract

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by severe bone destruction which has been associated with altered lipid metabolism. Apolipoprotein E (Apo E) is a lipoprotein crucial in lipid metabolism, mainly produced by macrophages. Moreover ApoE has been recently described as an important anti-inflammatory mediator regulating innate immunity and bone turnover.

Objectives In the present study we investigated the role of Apo E in inflammation and bone destruction during antigen-induced arthritis (AIA).

Methods Experimental arthritis (AIA) was induced by injection of 60 μg mBSA into the right knee joint of ApoE–/– and wild type (WT) control mice previously immunized with mBSA/CFA.

Joint swelling was measured by uptake of 99mTechnecium (99mTc) and expressed as a ratio of the uptake in right (injected) and the left (non injected) knee joint. Humoral immunity (mBSA antibody titer) was measured by ELISA. Joint inflammation and bone erosion were measured by histological analysis using an arbitrary scale from 0 to 3. TRAP+ cells were determined using immunohistochemistry.

Results ApoE–/– mice showed significantly less joint swelling at day 1, 3 and 7 after AIA induction compared to WT controls (21%, 17%, 18% lower, respectively). Serum mBSA antibody levels (total IgG, IgG1, IgG2a and IgG2b) are comparable between the two immunized mouse strains. At day 21, histology of the knee joints showed less infiltration of inflammatory cells (25% lower) and decreased bone erosion in the ApoE–/– mice compared to WT controls (25% lower from 1.5±0.2 to 1.1 ±0.1). In line with that, ApoE–/– mice showed a reduction of the number of osteoclasts present at the area of resorption within the arthritic knee joints (36% lower from 20±4 osteoclasts/section in WT mice to 12±5 in ApoE–/– mice), as measured by image analysis of TRAP staining.

Conclusions ApoE aggravates bone destruction within the knee joints during AIA by increasing influx of inflammatory cells within the synovium and elevating the number of resorbing osteoclasts on the bone surface.

Disclosure of Interest None declared

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