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Updated: Jul 9, 2026

Osteoclast Derivation from Mouse Bone Marrow
Published on: November 6, 2014
Treg cells suppress osteoclast formation: a new link between the immune system and bone
Mario M Zaiss1, Roland Axmann, Jochen Zwerina
1Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, Erlangen, Germany.
Objective:
To investigate whether Treg cells can suppress osteoclast differentiation, and to define a new potential link between the immune system and the skeleton.
Methods:
Regulatory CD4+,CD25+,Foxp3+ T cells were isolated and purified from the spleen and cocultured with CD11b+ osteoclast precursor cells isolated from bone marrow. Osteoclastogenesis and bone erosion were assessed by tartrate-resistant acid phosphatase staining and pit resorption assay, respectively. In addition, Transwell experiments and cytokine-blocking experiments were performed to define the mechanisms of interaction between Treg cells and osteoclasts.
Results:
CD4+,CD25+,Foxp3+ T cells, but not CD4+,CD25- T cells, dose dependently inhibited macrophage colony-stimulating factor- and RANKL-dependent osteoclast formation. Pit formation was inhibited by up to 80% when Treg cells were added. The blockade of osteoclast formation was not based on the alteration of RANKL/osteoprotegerin balance but was essentially dependent on direct cell-cell contact via CTLA-4. Treg cell-mediated expression of transforming growth factor beta, interleukin-4 (IL-4), and IL-10 contributed but was not essential to the inhibitory effect on osteoclastogenesis.
Conclusion:
These data show that CD4+,CD25+,Foxp3+ Treg cells suppress osteoclast formation, provide a new link between the immune system and bone, and extend our knowledge on regulation of bone homeostasis by the immune system.
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