TY - JOUR
T1 - Cadherin-mediated cell-cell adhesion and signaling in the skeleton
AU - Marie, Pierre J.
AU - Haÿ, Eric
AU - Modrowski, Dominique
AU - Revollo, Leila
AU - Mbalaviele, Gabriel
AU - Civitelli, Roberto
N1 - Funding Information:
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).
Funding Information:
Roberto Civitelli receives grant support from Amgen and Pfizer, and owns stock of Eli-Lilly, Merck, and Amgen. All other authors state they have no conflict of interest.
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Bone formation
KW - Cadherins
KW - Cell-cell adhesion
KW - Osteoblast differentiation
KW - Wnt/β-catenin signaling
UR - http://www.scopus.com/inward/record.url?scp=84893713853&partnerID=8YFLogxK
U2 - 10.1007/s00223-013-9733-7
DO - 10.1007/s00223-013-9733-7
M3 - Review article
C2 - 23657489
AN - SCOPUS:84893713853
SN - 0171-967X
VL - 94
SP - 46
EP - 54
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 1
ER -