[PDF][PDF] Calcineurin/NFAT signaling in osteoblasts regulates bone mass

MM Winslow, M Pan, M Starbuck, EM Gallo, L Deng… - Developmental cell, 2006 - cell.com
MM Winslow, M Pan, M Starbuck, EM Gallo, L Deng, G Karsenty, GR Crabtree
Developmental cell, 2006cell.com
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 (NFATc1 nuc) in osteoblasts develop high bone mass. NFATc1 nuc
mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and …
Summary
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.
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