CD115+ Osteoclast Precursors Arise before Clinical Onset of Arthritis and Are Regulated By Proinflammatory Cytokines

Antonia Puchner¹, Victoria Saferding², Eliana Goncalves-Alves³, Silvia Hayer⁴, Harald Leiss¹, Josef Smolen⁵, Kurt Redlich⁶ and Stephan Blüml¹, ¹Department of Rheumatology, Medical University of Vienna, Vienna, Austria, ²Rheumatology, Medical University of Vienna, Vienna, Austria, ³rheumatology, Medical University of Vienna, Vienna, Austria, ⁴Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria, ⁵Department of Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria, ⁶Division of Rheumatology, Medical University of Vienna, Vienna, Austria

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Cytokines and osteoclasts

Session Information

Title: Biology and Pathology of Bone and Joint: Osteoclasts, Osteoblasts and Bone Remodeling

Session Type: Abstract Submissions (ACR)

Background/Purpose

Bone erosions and systemic bone loss in rheumatoid arthritis patients results from an increased activity of osteoclasts, 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 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⁺CD115⁺ cells are elevated in blood before the onset of clinical symptoms and remain elevated throughout. In particular, a certain subset of CD11b⁺ myeloid cells that express intermediate levels of Ly6G expand in blood, spleen and bone marrow during arthritis. Of these, 89% express CD115, the MCSF-receptor. The increase of this population is not only observed in TNF-driven arthritis, but also in K/BxN arthritis. 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. After sorting this cells both subsets were able to form mature osteoclasts in vitro.

Conclusion

CD115⁺ CD11b⁺ cells with osteoclastogenic potential increase during inflammatory arthritis. This process, at least in TNF-driven arthritis is regulated by proinflammatory cytokines IL-1 and or IL-6. Elevated numbers of these cells can be detected before clinical onset of disease and therefore may provide a biomarker for inflammatory arthritis.

Disclosure:

A. Puchner,
None;

V. Saferding,
None;

E. Goncalves-Alves,
None;

S. Hayer,
None;

H. Leiss,
None;

J. Smolen,
None;

K. Redlich,
None;

S. Blüml,
None.

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