Wnt signaling in osteoblasts and bone diseases

Jennifer J Westendorf, Rachel A. Kahler, Tania M. Schroeder

Research output: Contribution to journalArticle

586 Citations (Scopus)

Abstract

Recent revelations that the canonical Wnt signaling pathway promotes postnatal bone accrual are major advances in our understanding of skeletal biology and bring tremendous promise for new therapeutic treatments for osteoporosis and other diseases of altered bone mass. Wnts are soluble glycoproteins that engage receptor complexes composed of Lrp5/6 and Frizzled proteins. A subgroup of Wnts induces a cascade of intracellular events that stabilize β-catenin, facilitating its transport to nuclei where it binds Lef1/Tcf transcription factors and alters gene expression to promote osteoblast expansion and function. Natural extracellular Wnt antagonists, Dickkopfs and secreted frizzled-related proteins, impair osteoblast function and block bone formation. In several genetic disorders of altered skeletal mass, mutations in LRP5 create gain-of-function or loss-of-function receptors that are resistant to normal regulatory mechanisms and cause higher or lower bone density, respectively. In this review, we summarize the available molecular, cellular, and genetic data that demonstrate how Lrp5 and other components of the Wnt signaling pathway influence osteoblast proliferation, function, and survival. We also discuss regulatory mechanisms discovered in developmental and tumor models that may provide insights into novel therapies for bone diseases.

Original languageEnglish (US)
Pages (from-to)19-39
Number of pages21
JournalGene
Volume341
Issue number1-2
DOIs
StatePublished - Oct 27 2004
Externally publishedYes

Fingerprint

Wnt Signaling Pathway
Bone Diseases
Osteoblasts
Frizzled Receptors
Catenins
Inborn Genetic Diseases
Osteogenesis
Bone Density
Osteoporosis
Molecular Biology
Glycoproteins
Transcription Factors
Gene Expression
Bone and Bones
Mutation
Therapeutics
Neoplasms

Keywords

  • β-catenin
  • Dkk
  • Lef1
  • Lrp5
  • Sfrp
  • Tcf

ASJC Scopus subject areas

  • Genetics

Cite this

Wnt signaling in osteoblasts and bone diseases. / Westendorf, Jennifer J; Kahler, Rachel A.; Schroeder, Tania M.

In: Gene, Vol. 341, No. 1-2, 27.10.2004, p. 19-39.

Research output: Contribution to journalArticle

Westendorf, JJ, Kahler, RA & Schroeder, TM 2004, 'Wnt signaling in osteoblasts and bone diseases', Gene, vol. 341, no. 1-2, pp. 19-39. https://doi.org/10.1016/j.gene.2004.06.044
Westendorf, Jennifer J ; Kahler, Rachel A. ; Schroeder, Tania M. / Wnt signaling in osteoblasts and bone diseases. In: Gene. 2004 ; Vol. 341, No. 1-2. pp. 19-39.
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