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Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival.
Cited 50 time in
Web of Science
Cited 51 time in Scopus
- Authors
- Issue Date
- 2012-12
- Publisher
- Rockefeller University Press
- Citation
- JOURNAL OF CELL BIOLOGY Vol.199 No.7, pp. 1145-1158
- Keywords
- 의약학
- Abstract
- The precise regulation of Ca2+ dynamics is crucial
for proper differentiation and function of osteoclasts.
Here we show the involvement of plasma
membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 in osteoclastogenesis.
In immature/undifferentiated cells, PMCAs
inhibited receptor activator of NF-B ligand–induced
Ca2+ oscillations and osteoclast differentiation in vitro.
Interestingly, nuclear factor of activated T cell c1 (NFATc1)
directly stimulated PMCA transcription, whereas the
PMCA-mediated Ca2+ efflux prevented NFATc1 activation,
forming a negative regulatory loop. PMCA4 also
had an anti-osteoclastogenic effect by reducing NO, which facilitates preosteoclast fusion. In addition to their
role in immature cells, increased expression of PMCAs in
mature osteoclasts prevented osteoclast apoptosis both
in vitro and in vivo. Mice heterozygous for PMCA1 or null
for PMCA4 showed an osteopenic phenotype with more
osteoclasts on bone surface. Furthermore, PMCA4 expression
levels correlated with peak bone mass in premenopausal
women. Thus, our results suggest that PMCAs
play important roles for the regulation of bone homeostasis
in both mice and humans by modulating Ca2+ signaling
in osteoclasts.
- ISSN
- 0021-9525
- Language
- English
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