IBMS BoneKEy | Perspective

N-Cadherin-Wnt connections and the control of bone formation

Pierre J Marie

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DOI:10.1138/20090372

Abstract

Cadherins are calcium-dependent cell adhesion molecules that play major roles during morphogenesis and tissue formation. Notably, the cell adhesion N-cadherin is an important regulator of chondrogenesis and osteogenesis. One recognized mechanism by which N-cadherin may promote osteoblast differentiation is by increasing cell-cell adhesion, resulting in activation of signals that promote osteoblast phenotypic gene expression. Cadherins can also trigger intracellular signals by interacting with the Wnt signaling pathway. In particular, cadherins can interact with β-catenin at the cell membrane, resulting in β-catenin sequestration, reduction of the cytosolic β-catenin pool and inhibition of Wnt signaling. Recent data provide another mechanism by which N-cadherin may control osteoblast function: N-cadherin was found to interact with the Wnt-co-receptors LRP5 or LRP6 in osteoblasts in vitro and in vivo. This interaction promotes β-catenin degradation, resulting in reduced Wnt signaling, decreased osteoblast differentiation and bone formation, and delayed bone accrual in mice. These data highlight the important crosstalk between cell adhesion and Wnt signaling molecules that impact osteoblast function, bone formation and bone mass.

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