title: Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling.
abstract: Matrix metalloproteinase-20 (MMP20) is expressed by ameloblasts in developing teeth and MMP20 mutations cause enamel malformation. We established a stably transfected Tet-Off Mmp20-inducible ameloblast-lineage cell line and found that MMP20 expression promoted cell invasion. Previously, we engineered transgenic mice (Tg) that drive Mmp20 expression and showed that Mmp20(+/+)Tg mice had soft enamel. Here we asked if Mmp20 overexpression disrupts ameloblast function. Incisors from Mmp20(+/+) mice expressing the Mmp20 Tg had a striking cell infiltrate which nearly replaced the entire enamel layer. A thin layer of enamel-like material remained over the dentin and at the outer tooth surface, but between these regions were invading fibroblasts and epithelial cells that surrounded ectopic bone-like calcifications. Mmp20(+/+)Tg mice had decreased enamel organ cadherin levels compared to the Mmp20 ablated and WT mice and, instead of predominantly locating adjacent to the ameloblast cell membrane, β-catenin was predominantly present within the nuclei of invading cells. Our data suggest that increased cadherin cleavage by transgenic MMP20 in the WT background releases excess β-catenin, which translocates to ameloblast nuclei to promote cell migration/invasion. Therefore, we conclude that MMP20 plays a role in normal ameloblast migration through tightly controlled Wnt signaling and that MMP20 overexpression disrupts this process.
authors.affiliation: Division of Biosciences, Ohio State University, College of Dentistry, Columbus, Ohio 43210, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shin
authors.affiliation: Division of Biosciences, Ohio State University, College of Dentistry, Columbus, Ohio 43210, USA.
authors.forename: Maiko
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Dept. of Mineralized Tissue Biology and Harvard School of Dental Medicine, The Forsyth Institute, Cambridge, MA, 02142, USA.
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Anatomy &Cell Biology, Facility for Electron Microscopy Research, McGill University, Montreal, QC, H3A 0C7, Canada.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Division of Biosciences, Ohio State University, College of Dentistry, Columbus, Ohio 43210, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Bartlett
mesh_terms: D000565:Ameloblasts / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003743:Dental Enamel / Q000196:embryology* / Q000473:pathology; D053519:Matrix Metalloproteinase 20 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D014070:Tooth / Q000196:embryology*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051176:beta Catenin; D053519:Matrix Metalloproteinase 20; C507113:Mmp20 protein, mouse