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J Orthop Res. 2012 Nov;30(11):1746-52. doi: 10.1002/jor.22153. Epub 2012 May 21.

E-cadherin upregulates expression of matrix macromolecules aggrecan and collagen II in the intervertebral disc cells through activation of the intracellular BMP-Smad1/5 pathway.

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1
Emory Spine Center, Emory University School of Medicine and VA Medical Center, VA Research Building, Atlanta, GA 30033, USA. zwang084@gmail.com

Abstract

E-cadherin is a transmembrane protein that mediates cell-cell adhesion and cell-matrix interaction. Although the E-cadherin has been shown to mediate a broad-ranging cellular signals and functions, its effects on matrix metabolism of intervertebral discs (IVDs) are unknown. In this study, we investigated the effects of E-cadherin on IVD matrix synthesis using pharmacological and molecular biology methods. We showed that high levels of the E-cadherin are expressed in rabbits IVD cells. Our study indicates that the ectopic expression of E-cadherin can stimulate matrix anabolism of the IVD cells, which was evidenced by increased expression of the matrix macromolecules aggrecan and collagen II. We found that E-cadherin induces the expression of BMP-4 and BMP-7 genes and enhances Smad1/5 phosphorylation. Blocking BMP activity uses noggin suppressed E-cadherin-mediated upregulation of aggrecan and collagen II. Moreover, inhibition of Smad1/5 phosphorylation by dorsomorphin significantly repressed the E-cadherin induced expression of aggrecan and collagen II at the both mRNA and protein levels. Together this study demonstrates that the E-cadherin stimulates the synthesis of IVD matrix macromolecules aggrecan and collagen II through the induction of BMP genes and enhancement of the Smad1/5 phosphorylation. Thus E-cadherin may have value in the treatment of degenerated discs.

PMID:
22615104
DOI:
10.1002/jor.22153
[Indexed for MEDLINE]
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