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Calcium Signaling in Osteoclast Differentiation and Bone Resorption

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Calcium Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 740))

Abstract

Calcium (Ca2+) signaling controls multiple cellular functions and is regulated by the release of Ca2+ from internal stores and its entry from the extracellular fluid. Ca2+ signals in osteoclasts are essential for diverse cellular functions including differentiation, bone resorption and gene transcription. Recent studies have highlighted the importance of intracellular Ca2+ signaling for osteoclast differentiation. Receptor activator of NF-κB ligand (RANKL) signaling induces oscillatory changes in intracellular Ca2+ concentrations, resulting in Ca2+/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 Ca2+ oscillation involved not only repetitive intracellular Ca2+ release from inositol 1, 4, 5-triphosphate channels in Ca2+ store sites, but also via store-operated Ca2+ entry and Ca2+ entry via transient receptor potential V channels during osteoclast differentiation. Ca2+-regulatory cytokines and elevation of extracellular Ca2+ concentrations have been shown to increase intracellular Ca2+ concentrations ([Ca2+]i) in mature osteoclasts, regulating diverse cellular functions. RANKL-induced [Ca2+]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, Ca2+ signaling activates differentiation in osteoclast precursors but suppresses resorption in mature osteoclasts. This chapter focuses on the roles of long-term Ca2+ oscillations in differentiation and of short-term Ca2+ increase in osteoclastic bone resorption activity.

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Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (20390475) and the Strategic Study Base Formation Support Business (S1001059).

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  1. Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, 814-0133, Japan

    Hiroshi Kajiya

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Correspondence to Hiroshi Kajiya .

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  1. , Department of Clinical Sciences and Educ, Karolinska Institutet, Tulegatan 26, Stockholm, SE-118 83, Sweden

    Md. Shahidul Islam

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Kajiya, H. (2012). Calcium Signaling in Osteoclast Differentiation and Bone Resorption. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 740. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2888-2_41

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