title: Calcium signaling in osteoclast differentiation and bone resorption.
abstract: Calcium (Ca(2+)) signaling controls multiple cellular functions and is regulated by the release of Ca(2+) from internal stores and its entry from the extracellular fluid. Ca(2+) signals in osteoclasts are essential for diverse cellular functions including differentiation, bone resorption and gene transcription. Recent studies have highlighted the importance of intracellular Ca(2+) signaling for osteoclast differentiation. Receptor activator of NF-κB ligand (RANKL) signaling induces oscillatory changes in intracellular Ca(2+) concentrations, resulting in Ca(2+)/calcineurin-dependent dephosphorylation and activation of nuclear factor of activated T cells c1 (NFATc1), which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. Recently, some reports indicated that RANKL-induced Ca(2+) oscillation involved not only repetitive intracellular Ca(2+) release from inositol 1, 4, 5-triphosphate channels in Ca(2+) store sites, but also via store-operated Ca(2+) entry and Ca(2+) entry via transient receptor potential V channels during osteoclast differentiation. Ca(2+)-regulatory cytokines and elevation of extracellular Ca(2+) concentrations have been shown to increase intracellular Ca(2+) concentrations ([Ca(2+)](i)) in mature osteoclasts, regulating diverse cellular functions. RANKL-induced [Ca(2+)](i) increase has been reported to inhibit cell motility and the resorption of cytoskeletal structures in mature osteoclasts, resulting in suppression of bone-resorption activity. In conclusion, Ca(2+) signaling activates differentiation in osteoclast precursors but suppresses resorption in mature osteoclasts. This chapter focuses on the roles of long-term Ca(2+) oscillations in differentiation and of short-term Ca(2+) increase in osteoclastic bone resorption activity.
authors.affiliation: Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0133, Japan. kajiya@college.fdcnet.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiya
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D006801:Humans; D050778:NFATC Transcription Factors / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology*; D050916:TRPV Cation Channels / Q000502:physiology
chemical_list: D015220:Calcium Channels; D050778:NFATC Transcription Factors; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D002118:Calcium