Essential role of β-catenin in postnatal bone acquisition

Sheri L. Holmen, Cassandra R. Zylstra, Aditi Mukherjee, Robert E. Sigler, Marie Claude Faugere, Mary L. Bouxsein, Lianfu Deng, Thomas L. Clemens, Bart O. Williams

Research output: Contribution to journalArticle

455 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21162-21168
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number22
DOIs
Publication statusPublished - Jun 3 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Holmen, S. L., Zylstra, C. R., Mukherjee, A., Sigler, R. E., Faugere, M. C., Bouxsein, M. L., ... Williams, B. O. (2005). Essential role of β-catenin in postnatal bone acquisition. Journal of Biological Chemistry, 280(22), 21162-21168. https://doi.org/10.1074/jbc.M501900200