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Osteoimmunology: evolving concepts in bone–immune interactions in health and disease


In terrestrial vertebrates, bone tissue constitutes the ‘osteoimmune’ system, which functions as a locomotor organ and a mineral reservoir as well as a primary lymphoid organ where haematopoietic stem cells are maintained. Bone and mineral metabolism is maintained by the balanced action of bone cells such as osteoclasts, osteoblasts and osteocytes, yet subverted by aberrant and/or prolonged immune responses under pathological conditions. However, osteoimmune interactions are not restricted to the unidirectional effect of the immune system on bone metabolism. In recent years, we have witnessed the discovery of effects of bone cells on immune regulation, including the function of osteoprogenitor cells in haematopoietic stem cell regulation and osteoblast-mediated suppression of haematopoietic malignancies. Moreover, the dynamic reciprocal interactions between bone and malignancies in remote organs have attracted attention, extending the horizon of osteoimmunology. Here, we discuss emerging concepts in the osteoimmune dialogue in health and disease.

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We thank K. Okamoto, T. Nitta, N. Komatsu and A. Terashima for providing helpful discussions during preparation of this manuscript. This work was supported in part by a grant for the Grants-in-Aid for Specially Promoted Research (15H05703) and the Research Fellowship for Young Scientists (18J00744) from the Japan Society for the Promotion of Science (JSPS).

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The authors contributed equally to all aspects of the article.

Correspondence to Hiroshi Takayanagi.

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Multinucleated cell of haematopoietic origin that resorbs bone via acid decalcification and proteolytic degradation.


Specialized mesenchymal cells that create bone by secreting bone matrix proteins and promoting mineralization.


Bone matrix-embedded cells that originate from osteoblasts, functioning as a commander of bone metabolism by controlling osteoblasts and osteoclasts.

Myeloid-derived suppressor cells

(MDSCs). Immature myeloid cells that have the capacity to suppress T cell responses.

Bone marrow mesenchymal stromal cells

Bone marrow cells of mesenchymal origin that contain heterogeneous populations of cells, including mesenchymal stem cells.

Pathogen-associated molecular patterns

(PAMPs). Microorganism-derived molecular structures that are recognized by pattern recognition receptors expressed on innate immune cells.

Danger-associated molecular patterns

(DAMPs). Cell-derived endogenous molecules that are released upon tissue damage and stimulate pattern recognition receptors expressed on innate immune cells.

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Fig. 1: Co-evolution of immune and skeletal systems.
Fig. 2: Osteoclast signalling network.
Fig. 3: Contributions of bone cells to immune regulation.
Fig. 4: Reciprocal interactions of bone and immune cells in systemic diseases.
Fig. 5: Molecular mechanisms of bone destruction in RA.
Fig. 6: Host defence against oral microorganisms through osteoimmune interplay.