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Calcified Tissue International

, Volume 94, Issue 1, pp 46–54 | Cite as

Cadherin-Mediated Cell–Cell Adhesion and Signaling in the Skeleton

  • Pierre J. Marie
  • Eric Haÿ
  • Dominique Modrowski
  • Leila Revollo
  • Gabriel Mbalaviele
  • Roberto Civitelli
Original Research

Abstract

Direct cell-to-cell interactions via cell adhesion molecules, in particular cadherins, are critical for morphogenesis, tissue architecture, and cell sorting and differentiation. Partially overlapping, yet distinct roles of N-cadherin (cadherin-2) and cadherin-11 in the skeletal system have emerged from mouse genetics and in vitro studies. Both cadherins are important for precursor commitment to the osteogenic lineage, and genetic ablation of Cdh2 and Cdh11 results in skeletal growth defects and impaired bone formation. While Cdh11 defines the osteogenic lineage, persistence of Cdh2 in osteoblasts in vivo actually inhibits their terminal differentiation and impairs bone formation. The action of cadherins involves both cell–cell adhesion and interference with intracellular signaling, and in particular the Wnt/β-catenin pathway. Both cadherin-2 and cadherin-11 bind to β-catenin, thus modulating its cytoplasmic pools and transcriptional activity. Recent data demonstrate that cadherin-2 also interferes with Lrp5/6 signaling by sequestering these receptors in inactive pools via axin binding. These data extend the biologic action of cadherins in bone forming cells, and provide novel mechanisms for development of therapeutic strategies aimed at enhancing bone formation.

Keywords

Bone formation Cadherins Cell–cell adhesion Osteoblast differentiation Wnt/β-catenin signaling 

Notes

Acknowledgments

Supported in part by Grants from the European Commission FP6 and FP7 research funding programs (LSHM-CT-2003-503020, HEALTH-F2-2008-201099 to PJM), the United States National Institutes of Health (AR055913, AR056678 to RC); and funds from the Société Française de Rhumatologie (to PJM) and the Barnes-Jewish Foundation (to RC).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Pierre J. Marie
    • 1
    • 2
  • Eric Haÿ
    • 1
    • 2
  • Dominique Modrowski
    • 1
    • 2
  • Leila Revollo
    • 3
  • Gabriel Mbalaviele
    • 3
  • Roberto Civitelli
    • 3
  1. 1.Laboratory of Osteoblast Biology and PathologyInserm UMR-606, Hôpital LariboisièreParis Cedex 10France
  2. 2.Université Paris Diderot, Sorbonne Paris Cité, UMR-606ParisFrance
  3. 3.Division of Bone and Mineral Diseases, Department of Internal MedicineWashington University in St. LouisSt. LouisUSA

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