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Phenotypic and functional characterization of osteoclast progenitors in circulatory and synovial compartments of patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is marked by the persistent inflammation and osteodestruction, causing progressive disability. Osteoclast progenitors (OCPs) represent a subpopulation of peripheral blood monocytes and have been shown to be present in healthy subjects and arthritic patients. The aim of our study was to determine the phenotype, frequency and osteoclastogenic potential of OCPs in the peripheral blood and synovial fluid of RA patients in response to anti-TNF therapy. Mononuclear cells were isolated from peripheral blood of healthy controls and RA patients, after obtaining approval from the Ethical Committee and informed consent from patients. In addition, peripheral blood and synovial fluid samples were collected from RA patients prior and in the follow- up of TNF-blockage treatment. The phenotype of monocyte subpopulations was determined within mononuclear cells by flow cytometry using the following markers: CD3, CD11b, CD11c, CD14, CD16, CD19, CD56, CD115 and selected chemokine receptors. Monocyte subpopulations were then sorted and cultured with the addition of M-CSF and RANKL to induce osteoclast differentiation. Results were correlated with clinical data, including inflammatory indicators and variables describing disease activity and severity. We have verified that human peripheral blood osteoclastogenic population (expressing CD11b, CD14, CD115, CCR2) is significantly increased in RA, comprising three- times more (3 to 6%) of circulating mononuclear cells compared with healthy controls. The same population was found among synovial fluid monocytes. Both circulatory and synovial monocyte progenitors exhibit in vitro osteoclastogenic potential. Anti TNF-treatment was not able to significantly decrease the proportion of peripheral OCPs, and only transiently suppressed their differentiation potential in osteoclastogenic cultures. We concluded that the peripheral blood osteoclastogenic monocyte population has been specifically induced in RA, and possibly attracted to the synovial compartment. Anti-TNF treatment only transiently suppressed osteoclastogenic potential of peripheral OCPs, indicating that additional therapeutic modalities, besides TNF- blocking agents, should be considered for sustained antiresorptive effect.

osteoclast progenitors ; rheumatoid arthritis ; osteoimmunology

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