Wnt signaling as a therapeutic target for bone diseases

Luke H. Hoeppner, Frank J. Secreto, Jennifer J. Westendorf

Research output: Contribution to journalReview article

173 Scopus citations

Abstract

Background: There is a need to develop new bone anabolic agents because current bone regeneration regimens have limitations. The Wingless-type MMTV integration site (Wnt) pathway has emerged as a regulator of bone formation and regeneration. Objective: To review the molecular basis for Wnt pathway modulation and discuss strategies that target it and improve bone mass. Methods: Data in peer-reviewed reports and meeting abstracts are discussed. Results/conclusions: Neutralizing inhibitors of Wnt signaling have emerged as promising strategies. Small-molecule inhibitors of glycogen synthase kinase 3? increase bone mass, lower adiposity and reduce fracture risk. Neutralizing antibodies to Dickkopf 1, secreted Frizzled-related protein 1 and sclerostin produce similar outcomes in animal models. These drugs are exciting breakthroughs but are not without risks. The challenges include tissue-specific targeting and consequently, long-term safety.

Original languageEnglish (US)
Pages (from-to)485-496
Number of pages12
JournalExpert opinion on therapeutic targets
Volume13
Issue number4
DOIs
StatePublished - Apr 2009

Keywords

  • Dkk1
  • GSK-3
  • Osteoporosis
  • SOST
  • Sclerostin
  • Sfrp1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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