Bone Abstracts

Background and Objectives: Rheumatoid arthritis (RA) is a chronic disease characterized by severe bone destruction which has been associated with altered lipid metabolism. Apolipoprotein E (Apo E) is a lipoprotein mainly produced by macrophages. ApoE has been described as crucial in lipid metabolism but also as an important anti-inflammatory mediator regulating innate immunity and bone turnover. In the present study we investigated the role of Apo E in bone destruction during antigen-induced arthritis (AIA).

Methods: Experimental arthritis (AIA) was induced by injection of 60 μg mBSA into the 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) knee joint and the left (non injected). 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 level of specific anti mBSA (total IgG, IgG1, IgG2a and IgG2b) was comparable between the two 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). In line with that, ApoE^−/− mice revealed a reduction of the number of osteoclasts present at the resorbed area (36% lower), measured by image analysis of TRAP staining.

Conclusions: ApoE aggravates bone destruction in AIA by increasing influx of inflammatory cells within the synovium and the number of resorbing osteoclasts along the bone.