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Cadherins and Wnt signalling: a functional link controlling bone formation
1Laboratory of Osteoblast Biology and Pathology, INSERM UMR-606, Hôpital Lariboisière , Paris, France ; University Paris Diderot, Sorbonne Paris Cité , Paris, France.
Bonekey Reports
|January 15, 2014
Summary
Cadherins negatively regulate bone formation by inhibiting Wnt signaling through N-cadherin and LRP5/6 interactions. Disrupting this interaction enhances osteoblast activity and bone mass.
Area of Science:
- Cell Biology
- Molecular Biology
- Bone Biology
Background:
- Cadherins are crucial for cell adhesion and tissue development.
- In bone, cadherins influence osteoblast differentiation and Wnt signaling pathways.
Purpose of the Study:
- To investigate the crosstalk between N-cadherin and Wnt signaling in osteoblasts.
- To explore the therapeutic potential of modulating this interaction for bone formation.
Main Methods:
- Examined the interaction between N-cadherin and Wnt coreceptors LRP5/6 in osteoblasts.
- Assessed the impact of this interaction on Wnt/β-catenin signaling.
- Utilized a competitor peptide to disrupt the N-cadherin-LRP5/6 interaction in vivo.
Main Results:
- N-cadherin interaction with LRP5/6 reduces Wnt signaling by promoting β-catenin degradation.
- This crosstalk negatively affects osteoblast proliferation, differentiation, and survival, leading to reduced bone formation.
- Disrupting the N-cadherin-LRP5/6 interaction increased Wnt/β-catenin signaling and enhanced osteoblastogenesis and bone mass in mice.
Conclusions:
- N-cadherin and Wnt signaling crosstalk is a key regulator of osteoblast function and bone mass.
- Targeting the N-cadherin-LRP5/6 interaction offers a potential therapeutic strategy for increasing bone formation.
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