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The role of calcium release activated calcium channels in osteoclast differentiation
Author(s) -
Zhou Yandong,
Lewis Tricia L.,
Robinson Lisa J.,
Brundage Kathy M.,
Schafer Rosana,
Martin Karen H.,
Blair Harry C.,
Soboloff Jonathan,
Barnett John B.
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22423
Subject(s) - osteoclast , calcium , microbiology and biotechnology , chemistry , biology , biochemistry , receptor , organic chemistry
Osteoclasts are specialized macrophage derivatives that secrete acid and proteinases to mobilize bone for mineral homeostasis, growth, and replacement or repair. Osteoclast differentiation generally requires the monocyte growth factor m‐CSF and the TNF‐family cytokine RANKL, although differentiation is regulated by many other cytokines and by intracellular signals, including Ca 2+ . Studies of osteoclast differentiation in vitro were performed using human monocytic precursors stimulated with m‐CSF and RANKL, revealing significant loss in both the expression and function of the required components of store‐operated Ca 2+ entry over the course of osteoclast differentiation. However, inhibition of CRAC using either the pharmacological agent 3,4‐dichloropropioanilide (DCPA) or by knockdown of Orai1 severely inhibited formation of multinucleated osteoclasts. In contrast, no effect of CRAC channel inhibition was observed on expression of the osteoclast protein tartrate resistant acid phosphatase (TRAP). Our findings suggest that despite the fact that they are down‐regulated during osteoclast differentiation, CRAC channels are required for cell fusion, a late event in osteoclast differentiation. Since osteoclasts cannot function properly without multinucleation, selective CRAC inhibitors may have utility in management of hyperresorptive states. J. Cell. Physiol. 226: 1082–1089, 2011. © 2010 Wiley‐Liss, Inc.