ECTS2016 Poster Presentations Arthritis and other joint diseases: translational and clinical (11 abstracts)
Identifying cell populations coupling inflammation to osteoresorption in arthritis
Elvira Lazic Mosler 1, , Darja Flegar 1 , Alan Sucur 1 , Martina Fadljevic 1 , Tomislav Kelava 1 , Antonio Markotic 1 , Sanja Ivcevic 1 , Katerina Zrinski-Petrovic 1 , Vedran Katavic 1 , Danka Grcevic 1 & Natasa Kovacic 1
1University of Zagreb School of Medicine, Zagreb, Croatia; 2General Hospital Ivo Pedisic, Sisak, Croatia.
Rheumatoid arthritis (RA) is characterised by periarticular bone destruction leading to permanent disability. Some other forms of arthritis, such as arthritis in systemic lupus erythematosus (SLE), rarely produce bone lesions. Corresponding to that, inactivation of Fas produces a murine SLE-like phenotype, but alleviates bone loss during antigen-induced arthritis (AIA). Aim of this study was to identify cell populations differentially regulated in non-resorptive vs. resorptive arthritis by comparing the synovial and bone marrow cellular composition in Fas-deficient and wild-type mice with AIA.
After obtaining approval from the Ethical Committee, mice were immunized with methylated(m)BSA in complete Freund’s adjuvant, followed by intra-articular injection of mBSA. Five weeks post-immunization, arthritis was assessed by histology and μCT. After collagenase digestion and labelling, cellular phenotype was determined by flow cytometry for the following markers: CD3, CD4, CD8, CD11b, CD29, CD31, CD44, CD45, CD90.1, CD106, CD115, CD166, CD117, B220, Gr-1, Sca-1, and TER119.
Micro-CT confirmed pronounced decrease in epiphyseal subchondral trabecular bone volume in wt mice with AIA (22.31±3.74%), in comparison to control group (31.18±3.14%, P=0.002, t-test), and the decrease was absent in Fas −/− mice (29.57±3.07% in control vs. 27.98±4.08% in AIA, P=0.60, t-test). Proportions of B220+, CD3+ and CD11b+ cells were significantly increased (P=0.04, P=0.008, P=0.019, respectively, Kruskal-Wallis test), while the proportions of CD106+ and CD166+ non-haemopoietic cells were significantly decreased in the synovial compartment of wild-type mice with AIA (P=0.04, and P=0.05, respectively, Kruskal-Wallis test). In all mice with AIA, proportions of CD3+, CD11b+ and Gr-1+ cells were strongly negatively associated with bone volume (ρ<−0.60, P<0.05), whereas positive association was found for CD106+ and 166+ stromal cells (ρ>0.60, P<0.05).
Populations specifically altered in non-resorptive form of arthritis are potentially involved in coupling the inflammatory process to bone destruction. Further analysis of their molecular signatures may identify novel targets for counteracting osteoresorption induced by inflammation.
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