Osteoclasts, rheumatoid arthritis, and osteoimmunology.
OBJECTIVE
Osteoclasts are terminally differentiated cells of the monocyte/macrophage lineage that resorb bone matrix. Bone destruction in rheumatoid arthritis is mainly attributable to the abnormal activation of osteoclasts, and studies on activation of osteoclasts by the immune system have led to the new research field called osteoimmunology. This interdisciplinary field is very important to biologic research and to the treatment of diseases associated with the bone and immune systems.


RESULTS
The T-cell-mediated regulation of osteoclast differentiation is dependent on cytokines and membrane-bound factors expressed by T cells. The cross-talk between receptor activator of nuclear factor-kappaB ligand and interferon-gamma has been shown to be crucial for the regulation of osteoclast formation in arthritic joints. Recent studies indicate that an increasing number of immunomodulatory factors are associated with the regulation of bone metabolism: nuclear factor of activated T cells c1 has been shown to be the key transcription factor for osteoclastogenesis, the activation of which requires calcium signaling induced by the immunoglobulin-like receptors.


CONCLUSIONS
New findings in osteoimmunology will be instrumental in the development of strategies for research into the treatment of various diseases afflicting the skeletal and immune systems.
Sato
Kojiro
K
Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Japan.
Takayanagi
Hiroshi
H
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology*; D001862:Bone Resorption / Q000276:immunology / Q000503:physiopathology; D001842:Bone and Bones / Q000276:immunology*; D002454:Cell Differentiation; D006801:Humans; D010010:Osteoclasts / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology