Background Bone erosions and systemic bone loss in rheumatoid arthritis patients results from an increased activity of osteoclast, which are derived from precursor cells of the myeloid lineage. Although there is much known about the mechanisms regulating the formation and activation of mature osteoclasts, the identity of an osteoclast precursor population in and its regulation by inflammatory cytokines during arthritis is poorly understood.
Methods HTNFtg mice were clinically scored once per week for grip strength and swelling. In addition, blood was collected every other week starting on week 4. Mice were sacrificed at week 10 - blood, spleen and bone marrow were collected for flow cytometry analysis. IL1/IL6–/– were crossed into hTNFtg mice and blood was also analyzed. K/BxN Arthritis was induced in wild type mice, blood and spleen were collected 14 days after disease induction. Different monocyte subsets were Facs-sorted and cultured in the presence of RANKL and MCSF to induce osteoclasts
Results We show that during TNF-driven arthritis CD11b+ cells are elevated in blood spleen and bone marrow even before the onset of clinical symptoms and remain elevated throughout. In particular, a certain subset of myeloid cells, characterized by the expression of CD11b and LY6C as well as LY6G, increases in blood, spleen and bone marrow during arthritis. After sorting, these cells are particularly able to form mature osteoclasts in vitro. The increase of this myeloid population is not only observed in TNF-driven arthritis, but can also in K/BxN serum transfer arthritis. We furthermore demonstrate that IL-1 and/or IL-6 importantly regulate the expansion of these cells as in IL1/IL-6 double deficient hTNFtg we did not detect an elevation of this subset.
Conclusions Osteoclast precursors arise from a monocyte subpopulation that is specifically increased during inflammatory arthritis. Elevated numbers of these cells can be detected before clinical onset of disease and therefore may provide a biomarker for inflammatory arthritis.
Disclosure of Interest None declared