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NFATc1 Induces Osteoclast Fusion Via Up-Regulation of Atp6v0d2 and the Dendritic Cell-Specific Transmembrane Protein (DC-STAMP)

Kim, Kabsun, Lee, Seoung-Hoon, Ha Kim, Jung, Choi, Yongwon, Kim, Nacksung·2008·Molecular Endocrinology
DOI 10.1210/me.2007-0237
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Abstract

NFATc1 has been characterized as a master regulator of nuclear factor κB ligand-induced osteoclast differentiation. Herein, we demonstrate a novel role for NFATc1 as a positive regulator of nuclear factor κB ligand-mediated osteoclast fusion as well as other fusion-inducing factors such as TNF-α. Exogenous overexpression of a constitutively active form of NFATc1 in bone marrow-derived monocyte/macrophage cells (BMMs) induces formation of multinucleated osteoclasts as well as the expression of fusion-mediating molecules such as the d2 isoform of vacuolar ATPase Vo domain (Atp6v0d2) and the dendritic cell-specific transmembrane protein (DC-STAMP). Moreover, inactivation of NFATc1 by cyclosporin A treatment attenuates expression of Atp6v0d2 and DC-STAMP and subsequent fusion process of osteoclasts. We show that NFATc1 binds to the promoter regions of Atp6v0d2 and DC-STAMP in osteoclasts and directly induces their expression. Furthermore, overexpression of Atp6v0d2 and DC-STAMP rescues cell-cell fusion of preosteoclasts despite reduced NFATc1 activity. Our data indicate for the first time that the NFATc1/Atp6v0d2 and DC-STAMP signaling axis plays a key role in the osteoclast multinucleation process, which is essential for efficient bone resorption.

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Research works printed but not linked: 32

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Metadata

Authors
Kim, K., Lee, S.-H., Ha Kim, J., Choi, Y., & Kim, N.
Affiliations
  • National Research Laboratory for Regulation of Bone Metabolism and Disease (K.K., J.H.K., N.K.), Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea
  • Department of Pathology and Laboratory Medicine (S.-H.L., Y.C.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19014
Venue
Molecular Endocrinology
Publisher
The Endocrine Society
Published
2008-01-01
Volume
22
Issue
1
Pages
176-185
ISSN
  • 0888-8809
  • 1944-9917
DOI
10.1210/me.2007-0237
Cited by
421
References
5
Language
en

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CoChat. (2026). Citation check: NFATc1 Induces Osteoclast Fusion Via Up-Regulation of Atp6v0d2 and the Dendritic Cell-Specific Transmembrane Protein (DC-STAMP). https://app.cochat.ai/papers/10.1210/me.2007-0237
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Kim, K., Lee, S.-H., Ha Kim, J., Choi, Y., & Kim, N. (2008). NFATc1 Induces Osteoclast Fusion Via Up-Regulation of Atp6v0d2 and the Dendritic Cell-Specific Transmembrane Protein (DC-STAMP). Molecular Endocrinology. https://doi.org/10.1210/me.2007-0237

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