engleski

Myeloid-specific molecular mediators of subchondral bone damage in antigen-induced arthritis

Introduction: Rheumatoid arthritis (RA) is marked by subchondral bone destruction, joint deformations and disability. Available therapeutics improve the prognosis, but with limited effect on bone destruction. Using antigen- induced arthritis (AIA), animal model of RA, we found that mice deficient for Fas gene (Fas-/-) develop non- destructive arthritis, marked by lower frequency of myeloid cells in joints. We aim to identify mediators of bone resorption in arthritis, by analyzing differentially expressed genes in sorted myeloid population from wild-type (WT) and Fas -/- mice with AIA. Materials and methods: AIA was induced by intra-articular injection of methylated bovine serum albumin to immunized mice. Bone resorption was assessed by µCT. Synovial cells were released by collagenase, labeled with anti-mouse CD45-FITC, CD11b-PE, Gr1- PECy7, B220/CD3/NK1.1/CD31/TER119-APC, and CD51- APCeF780. CD11b+Gr-1+ population was sorted using BD FACSAria, RNA extracted by Trizol, and hybridized to Affymetrix ST 2.0 arrays. Differences in gene expression found on arrays were confirmed by qRT-PCR. Results: Synovial CD11b+Gr1+ cells were transcriptionally similar in Fas -/- and WT mice with AIA. Samples split into two hierarchical clusters consisting predominantly of Fas -/- or WT samples. WT-dominant cluster revealed up-regulated genes related to cell cycle progression and mitosis, suggesting higher proliferation. Mid1 and Erdr1 genes were downregulated in joints from Fas -/- mice with AIA, which was confirmed by PCR. Conclusions: Resorptive AIA is marked by higher myeloid proliferation potential. Mid1 gene is a potential novel mediator for targeting inflammation-mediated joint destruction in arthritis.

arthritis ; myeloid cells ; Midline 1

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