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.

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.