S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival.
- Kim, Hyung Joon; Prasad, Vikram; Hyung, Seok-Won; Lee, Zang Hee; Lee, Sang-Won; Bhargava, Aditi; Pearce, David; Lee, Youngkyun; Kim, Hong-Hee
- Issue Date
- Rockefeller University Press
- JOURNAL OF CELL BIOLOGY Vol.199 No.7, pp. 1145-1158
- 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