Purpose We aimed to assess osteoclastogenic potential of peripheral blood mononuclear cells (PBMC) and synovial fluid-derived mononuclear cells (SFMC) in different forms of arthritis and to correlate it with inflammatory mediators within intra-articular and circulatory compartments. Methods Paired PBMC and SFMC samples of patients with rheumatoid arthritis (RA; n =10) and psoriatic arthritis (PsA; n =10), and PBMC of healthy controls were cultured to assess osteoclastogenic potential by the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) and expression of OC-related genes (receptor activator of nuclear factor-κΒ (RANK), cFMS, and TRAP). Osteoclastogenesis was correlated with the arthritis-related inflammatory indicators in serum and synovial fluid (SF). Results Number of OCs differentiated from PBMC was significantly higher in RA and PsA compared with control, with RA having more OCs compared with PsA. There was no difference in SFMC OC number between arthritic patients, but RANK expression in OCs differentiated from SFMC was higher in PsA compared with RA. SF of PsA patients more potently induced OC differentiation from control CD3 + PBMC compared with RA, paralleled with higher RANK-ligand expression in PsA SFMC. Positive correlations of OC number with erythrocyte sedimentation rate, serum level of CCL2, and PBMC gene expression of interleukin-18 and Fas-ligand were observed. Conclusion Osteoclastogenic potential is systemically enhanced in patients with RA, paralleled by disordered systemic and local expression of proinflammatory mediators, whereas PsA involves specific deregulation in RANKL/RANK axis. Our study reveals arthritis-specific mediators associated with the form of arthritis, indicating clinical relevance for diagnosis and treatment.

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Background Collagen induced arthritis (CIA) is a mouse model for human rheumatoid arthritis (RA). Based on the observation that prolonged activation of the immune system causes bone loss we hypothesize that chronic inflammatory and immune responses promote osteoresorption by affecting osteoclast differentiation and/or altering their recruitment and homing. In adittion, changes in osteoblast differentiation and activity may also contribute to insufficient bone formation associated with bone loss in RA. Objectives Our aim was to characterize the osteoclastogenic potential of bone marrow- and peripheral-hematopoietic cells, and osteoblastogenic potential of bone marrow-derived stromal cells. Methods C57BL/6 mice were immunized with chicken type II collagen (CII). Circulating levels of anti-collagen antibodies IgG1 and IgG2a were determined in individual sera from nonarthritic and arthritic mice by ELISA. Hematopoietic cells from different sources (bone marrow, homogenized bone shafts, spleen, peripheral blood) were cultured with RANKL and M-CSF to stimulate osteoclast (OCL) differentiation. OCLs were detected as TRAP-positive multinucleated cells with 3 or more nuclei per cell. Osteoblast differentiation of bone marrow cells was induced by the addition of ascorbic acid, dexamethasone and β-glycerophosphate and analyzed by alkaline phosphatase (AP) activity and AP histochemistry. For flow-cytometry, a series of hematopoietic markers were used to characterize osteoclast progenitor (B220, CD3, NK1.1, CD115, CD117, CD11b), myeloid and lymphoid populations. Gene expression analysis for inflammatory, osteoclast and osteoblast specific genes was performed by qPCR. Results The mice that were immunized with CII develop arthritis with incidence of almost 100% and average clinical score 10±2.6. Anti-collagen antibodies IgG1 and IgG2a were only detected in arthritic group of mice. The number of differentiated OCLs from peripheral blood, spleen and bone-shaft derived cells was significantly higher (p<0.01, Student t-test) in CIA than in control mice. There was no significant difference in OCL numbers from bone marrow- derived cells. AP activity of osteoblast differentiated from bone marrow stromal cells of arthritic mice was significantly higher than AP activity of those derived from bone marrow stromal cells of nonarthritic mice. Flow cytometry showed more CD115+ cells within both CD11b-/low and CD11b+ populations in the periphery, indicating increased number of osteoclast progenitors in CIA compared with control mice. In addition, myeloid and B-lymphoid populations increased whereas NK cell population decreased in CIA. Gene expression analysis showed increased expression of IL-17 and cFms in blood cells and decreased expression of Runx2 in bone tissue. Conclusions Our results indicate that the peripheral-hematopoietic cells but not the bone marrow-hematopoietic cells of mice with CIA have higher number of OCL progenitors and greater osteoclastogenic potential than control mice. Disclosure of Interest None Declared

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