TY - JOUR
T1 - Essential role of β-catenin in postnatal bone acquisition
AU - Holmen, Sheri L.
AU - Zylstra, Cassandra R.
AU - Mukherjee, Aditi
AU - Sigler, Robert E.
AU - Faugere, Marie Claude
AU - Bouxsein, Mary L.
AU - Deng, Lianfu
AU - Clemens, Thomas L.
AU - Williams, Bart O.
PY - 2005/6/3
Y1 - 2005/6/3
N2 - Mutations in the Wnt co-receptor LRP5 alter bone mass in humans, but the mechanisms responsible for Wnts actions in bone are unclear. To investigate the role of the classical Wnt signaling pathway in osteogenesis, we generated mice lacking the β-catenin or adenomatous polyposis coli (Apc) genes in osteoblasts. Loss of β-catenin produced severe osteopenia with striking increases in osteoclasts, whereas constitutive activation of β-catenin in the conditional Apc mutants resulted in dramatically increased bone deposition and a disappearance of osteoclasts. In vitro, osteoblasts lacking the β-catenin gene exhibited impaired maturation and mineralization with elevated expression of the osteoclast differentiation factor, receptor activated by nuclear factor-κB ligand (RANKL), and diminished expression of the RANKL decoy receptor, osteoprotegerin. By contrast, Apc-deficient osteoblasts matured normally but demonstrated decreased expression of RANKL and increased osteoprotegerin. These findings suggest that Wnt/β-catenin signaling in osteoblasts coordinates postnatal bone acquisition by controlling the differentiation and activity of both osteoblasts and osteoclasts.
AB - Mutations in the Wnt co-receptor LRP5 alter bone mass in humans, but the mechanisms responsible for Wnts actions in bone are unclear. To investigate the role of the classical Wnt signaling pathway in osteogenesis, we generated mice lacking the β-catenin or adenomatous polyposis coli (Apc) genes in osteoblasts. Loss of β-catenin produced severe osteopenia with striking increases in osteoclasts, whereas constitutive activation of β-catenin in the conditional Apc mutants resulted in dramatically increased bone deposition and a disappearance of osteoclasts. In vitro, osteoblasts lacking the β-catenin gene exhibited impaired maturation and mineralization with elevated expression of the osteoclast differentiation factor, receptor activated by nuclear factor-κB ligand (RANKL), and diminished expression of the RANKL decoy receptor, osteoprotegerin. By contrast, Apc-deficient osteoblasts matured normally but demonstrated decreased expression of RANKL and increased osteoprotegerin. These findings suggest that Wnt/β-catenin signaling in osteoblasts coordinates postnatal bone acquisition by controlling the differentiation and activity of both osteoblasts and osteoclasts.
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U2 - 10.1074/jbc.M501900200
DO - 10.1074/jbc.M501900200
M3 - Article
C2 - 15802266
AN - SCOPUS:20444376156
SN - 0021-9258
VL - 280
SP - 21162
EP - 21168
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 22
ER -