The role of NFAT in osteoclast formation.
Osteoclasts are cells of monocyte-macrophage origin that degrade bone matrix. Receptor activator of NF-kappaB ligand (RANKL) induces osteoclast formation in the presence of macrophage-colony-stimulating factor (M-CSF) and costimulatory signals. RANKL induces activation of the TNF receptor-associated factor 6 (TRAF6) and c-Fos pathways, which lead to the osteoclast-specific event, that is, autoamplification of nuclear factor of activated T cells (NFAT)c1, the master transcription factor for osteoclast differentiation. Autoamplification of NFATc1 is dependent on the calcium signaling of immunoglobulin-like receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adaptors. In addition to the calcineurin-NFATc1 axis, calcium signaling activates the calmodulin-dependent kinase pathway, which also plays a critical role in osteoclast formation. Such advances in the understanding of the molecular mechanism of osteoclast differentiation are expected to lead to novel therapeutic approaches to bone diseases.
Takayanagi
Hiroshi
H
Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. taka.csi@tmd.ac.jp
D000818:Animals; D006801:Humans; D050778:NFATC Transcription Factors / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology*; D053245:RANK Ligand / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic
D050778:NFATC Transcription Factors; D053245:RANK Ligand