Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling

Masashi Shin, Maiko Suzuki, Xiaomu Guan, Charles E Smith, John D Bartlett

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)29492
JournalScientific Reports
Volume6
DOIs
StatePublished - Jul 11 2016
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 20
Ameloblasts
Dental Enamel
Catenins
Cadherins
Tooth
Enamel Organ
Dentin
Incisor
Cell Nucleus
Transgenic Mice
Cell Movement
Fibroblasts
Epithelial Cells
Cell Membrane
Bone and Bones
Cell Line
Mutation

Keywords

  • Ameloblasts/metabolism
  • Animals
  • Cadherins/metabolism
  • Cell Movement/physiology
  • Cells, Cultured
  • Dental Enamel/embryology
  • Matrix Metalloproteinase 20/biosynthesis
  • Mice
  • Mice, Transgenic
  • Tooth/embryology
  • Wnt Signaling Pathway/physiology
  • beta Catenin/metabolism

Cite this

Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling. / Shin, Masashi; Suzuki, Maiko; Guan, Xiaomu; Smith, Charles E; Bartlett, John D.

In: Scientific Reports, Vol. 6, 11.07.2016, p. 29492.

Research output: Contribution to journalArticle

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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.",
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