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

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. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1746–1752, 2012