The role of calcium release activated calcium channels in osteoclast differentiation

Yandong Zhou, Tricia L. Lewis, Lisa J. Robinson, Kathy M. Brundage, Rosana Schafer, Karen H. Martin, Harry C. Blair, Jonathan Soboloff, John B. Barnett

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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 Ca2+. 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 Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)1082-1089
Number of pages8
JournalJournal of Cellular Physiology
Volume226
Issue number4
DOIs
StatePublished - Apr 1 2011

Fingerprint

Osteoclasts
Calcium Channels
Calcium
Cytokines
Calcium Release Activated Calcium Channels
Cell Fusion
Macrophages
Acid Phosphatase
Minerals
Monocytes
Intercellular Signaling Peptides and Proteins
Bone
Homeostasis
Repair
Peptide Hydrolases
Fusion reactions
Pharmacology
Derivatives
Bone and Bones
Acids

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Zhou, Y., Lewis, T. L., Robinson, L. J., Brundage, K. M., Schafer, R., Martin, K. H., ... Barnett, J. B. (2011). The role of calcium release activated calcium channels in osteoclast differentiation. Journal of Cellular Physiology, 226(4), 1082-1089. https://doi.org/10.1002/jcp.22423
Zhou, Yandong ; Lewis, Tricia L. ; Robinson, Lisa J. ; Brundage, Kathy M. ; Schafer, Rosana ; Martin, Karen H. ; Blair, Harry C. ; Soboloff, Jonathan ; Barnett, John B. / The role of calcium release activated calcium channels in osteoclast differentiation. In: Journal of Cellular Physiology. 2011 ; Vol. 226, No. 4. pp. 1082-1089.
@article{6a8fa4158a9f4afdb92fe75f1e9103dd,
title = "The role of calcium release activated calcium channels in osteoclast differentiation",
abstract = "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 Ca2+. 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 Ca2+ 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.",
author = "Yandong Zhou and Lewis, {Tricia L.} and Robinson, {Lisa J.} and Brundage, {Kathy M.} and Rosana Schafer and Martin, {Karen H.} and Blair, {Harry C.} and Jonathan Soboloff and Barnett, {John B.}",
year = "2011",
month = "4",
day = "1",
doi = "10.1002/jcp.22423",
language = "English (US)",
volume = "226",
pages = "1082--1089",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "4",

}

Zhou, Y, Lewis, TL, Robinson, LJ, Brundage, KM, Schafer, R, Martin, KH, Blair, HC, Soboloff, J & Barnett, JB 2011, 'The role of calcium release activated calcium channels in osteoclast differentiation', Journal of Cellular Physiology, vol. 226, no. 4, pp. 1082-1089. https://doi.org/10.1002/jcp.22423

The role of calcium release activated calcium channels in osteoclast differentiation. / Zhou, Yandong; Lewis, Tricia L.; Robinson, Lisa J.; Brundage, Kathy M.; Schafer, Rosana; Martin, Karen H.; Blair, Harry C.; Soboloff, Jonathan; Barnett, John B.

In: Journal of Cellular Physiology, Vol. 226, No. 4, 01.04.2011, p. 1082-1089.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of calcium release activated calcium channels in osteoclast differentiation

AU - Zhou, Yandong

AU - Lewis, Tricia L.

AU - Robinson, Lisa J.

AU - Brundage, Kathy M.

AU - Schafer, Rosana

AU - Martin, Karen H.

AU - Blair, Harry C.

AU - Soboloff, Jonathan

AU - Barnett, John B.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - 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 Ca2+. 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 Ca2+ 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.

AB - 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 Ca2+. 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 Ca2+ 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.

UR - http://www.scopus.com/inward/record.url?scp=79251521476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251521476&partnerID=8YFLogxK

U2 - 10.1002/jcp.22423

DO - 10.1002/jcp.22423

M3 - Article

C2 - 20839232

AN - SCOPUS:79251521476

VL - 226

SP - 1082

EP - 1089

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 4

ER -