title: 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.
authors.affiliation: Emory Spine Center, Emory University School of Medicine and VA Medical Center, VA Research Building, Atlanta, GA 30033, USA. zwang084@gmail.com
authors.forename: Zili
authors.initials: Z
authors.lastname: Wang
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: William C
authors.initials: WC
authors.lastname: Hutton
authors.forename: Sangwook Tim
authors.initials: ST
authors.lastname: Yoon
mesh_terms: D053674:Aggrecans / Q000378:metabolism*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism*; D010766:Phosphorylation; D011817:Rabbits; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053674:Aggrecans; D019485:Bone Morphogenetic Proteins; D015820:Cadherins; D024043:Collagen Type II; D051898:Smad1 Protein; D051902:Smad5 Protein