Exploiting the WNT Signaling Pathway for Clinical Purposes

Curr Osteoporos Rep. 2017 Jun;15(3):153-161. doi: 10.1007/s11914-017-0357-0.

Abstract

Purpose of review: The goal of this paper is to evaluate critically the literature published over the past 3 years regarding the Wnt signaling pathway. The Wnt pathway was found to be involved in bone biology in 2001-2002 with the discovery of a (G171V) mutation in the lipoprotein receptor-related protein 5 (LRP5) that resulted in high bone mass and another mutation that completely inactivated Lrp5 function and resulted in osteoporosis pseudoglioma syndrome (OPPG). The molecular biology has been complex, and very interesting. It has provided many opportunities for exploitation to develop new clinical treatments, particularly for osteoporosis. More clinical possibilities include: treatments for fracture healing, corticosteroid osteoporosis, osteogenesis imperfecta, and others. In addition, we wish to provide historical information coming from distant publications (~350 years ago) regarding bone biology that have been confirmed by study of Wnt signaling.

Recent findings: A recent finding is the development of an antibody to sclerostin that is under study as a treatment for osteoporosis. Development of treatments for other forms of osteoporosis, such as corticosteroid osteoporosis, is also underway. The full range of the applications of the work is not yet been achieved.

Keywords: Lrp5; Mechanostat; Osteoporosis; Wnt; Wnt signaling; β-catenin.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics*
  • Molecular Targeted Therapy
  • Osteogenesis Imperfecta / genetics*
  • Osteoporosis / drug therapy*
  • Wnt Signaling Pathway / genetics*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • romosozumab
  • blosozumab

Supplementary concepts

  • Osteoporosis-pseudoglioma syndrome