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Int J Mol Med. 2014 Mar;33(3):565-72. doi: 10.3892/ijmm.2013.1607. Epub 2013 Dec 27.

Cell-cell adhesion through N-cadherin enhances VCAM-1 expression via PDGFRβ in a ligand-independent manner in mesenchymal stem cells.

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Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan.
Division of Oral Surgery, Department of Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan.
Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan.


Cell-cell adhesions induce various intracellular signals through hierarchical and synergistic molecular interactions. Recently, we demonstrated that a high cell density induces the expression of vascular cell adhesion molecule-1 (VCAM-1) through the nuclear factor-κB (NF-κB) pathway in human bone marrow-derived mesenchymal stem cells (MSCs). However, the specific molecules that activated the NF-κB pathway were not determined. In the present study, in experiments with receptor tyrosine kinase inhibitors, VCAM-1 expression was completely suppressed by platelet-derived growth factor (PDGF) receptor (PDGFR) inhibitors. In addition, VCAM-1 expression was significantly suppressed by knockdown with PDGFRβ siRNA, but not with PDGFRα siRNA. However, VCAM-1 expression did not increase following treatment with PDGF. The overexpression of N-cadherin, a structural molecule in adherence junctions in MSCs, promoted VCAM-1 expression and induced the marked phosphorylation of the intracellular signaling factor, Src. In addition, VCAM-1 expression and Src phosphorylation were reduced by the overexpression of a dominant negative mutant of N-cadherin. These results suggest that cell-cell adhesion, through N-cadherin, enhances the expression of VCAM-1 via PDGFRβ and the activation of Src in a ligand-independent manner in MSCs.

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