Calcineurin/NFAT Signaling in Osteoblasts Regulates Bone Mass

Monte M. Winslow, Minggui Pan, Michael Starbuck, Elena M. Gallo, Lei Deng, Gerard Karsenty, Gerald R. Crabtree

Research output: Contribution to journalArticlepeer-review

Abstract

Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1nuc) in osteoblasts develop high bone mass. NFATc1nuc mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1nuc mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts.

Original languageEnglish (US)
Pages (from-to)771-782
Number of pages12
JournalDevelopmental Cell
Volume10
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • DEVBIO
  • HUMDISEASE

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Calcineurin/NFAT Signaling in Osteoblasts Regulates Bone Mass'. Together they form a unique fingerprint.

Cite this