ArticleMolecular genetics & genomic medicine2016
MMP20, KLK4, and MMP20/KLK4 double null mice define roles for matrix proteases during dental enamel formation.
Article in Molecular genetics & genomic medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Integrative multi-omics and bioinformatic analysis ofThe Japanese dental science review · 2026Review
- NovelGenes · 2026Article
- NovelJournal of dental sciences · 2026Article
- Identification and elemental mapping of enamel minerals with electron energy-loss spectroscopy.RSC advances · 2025Article
- Article
- Expression ofInternational journal of molecular sciences · 2025Article
- Genetic Screening of a Nonsyndromic Amelogenesis Imperfecta Patient Cohort Using a Custom smMIP Reagent for Selective Enrichment of Target Loci.Human mutation · 2025Article
- The role of the TGF-β1 signaling pathway in the process of amelogenesis.Frontiers in physiology · 2025Review
- CRISPR/Cas9-Induced Fam83h Knock-out Leads to Impaired Wnt/β-Catenin Pathway and Altered Expression of Tooth Mineralization Genes in Mice.Iranian journal of biotechnology · 2023Article
- Association of KLK4 rs2235091 polymorphism with susceptibility to dental caries: a systematic review and meta-analysis.Frontiers in pediatrics · 2023Review
- Odontogenesis-Associated Phosphoprotein (ODAPH) Overexpression in Ameloblasts Disrupts Enamel Formation via Inducing Abnormal Mineralization of Enamel in Secretory Stage.Calcified tissue international · 2022Article
- Enamel defects in Acp4Scientific reports · 2022Article
- Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts.International journal of molecular sciences · 2022Article
- Mechanisms of Enamel Mineralization Guided by Amelogenin Nanoribbons.Journal of dental research · 2021Review
- MMP20-generated amelogenin cleavage products prevent formation of fan-shaped enamel malformations.Scientific reports · 2021Article
- Size changes in miR‑21 knockout mice: Geometric morphometrics on teeth, alveolar bone and mandible.Molecular medicine reports · 2021Article
- Review
- Odontogenesis-associated phosphoprotein truncation blocks ameloblast transition into maturation in OdaphScientific reports · 2021Article
- Dental malformations associated with biallelic MMP20 mutations.Molecular genetics & genomic medicine · 2020Article
- Tooth Enamel and its Dynamic Protein Matrix.International journal of molecular sciences · 2020Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Matrix metalloproteinase 20 (MMP20) and kallikrein-related peptidase 4 (KLK4) are secreted proteinases that are essential for proper dental enamel formation. We characterized and compared enamel formed in wild-type, Mmp20 (-/-), Klk4 (-/-), Mmp20 (+/-) Klk4 (+/-), and Mmp20 (-/-) Klk4 (-/-) mice using dissecting and light microscopy, backscattered scanning electron microscopy (bSEM), SEM, microcomputed tomography (μCT), and energy-dispersive X-ray analysis (EDX). Following eruption, fractures were observed on Mmp20 (-/-), Klk4 (-/-), Mmp20 (+/-) Klk4 (+/-), and Mmp20 (-/-) Klk4 (-/-) molars. Failure of the enamel in the Mmp20 (+/-) Klk4 (+/-) molars was unexpected and suggested that digenic effects could contribute to the etiology of amelogenesis imperfecta in humans. Micro-CT analyses of hemimandibles demonstrated significantly reduced high-density enamel volume in the Mmp20 (-/-) and Klk4 (-/-) mice relative to the wild-type, which was further reduced in Mmp20 (-/-) Klk4 (-/-) mice. bSEM images of 7-week Mmp20 (-/-) and Mmp20 (-/-) Klk4 (-/-) mandibular incisors showed rough, pitted enamel surfaces with numerous indentations and protruding nodules. The Mmp20 (+/-) and Mmp20 (+/-) Klk4 (+/-) incisors showed prominent, evenly spaced, horizontal ridges that were more distinct in Mmp20 (+/-) Klk4 (+/-) incisors relative to Mmp20 (+/-) incisors due to the darkening of the valleys between the ridges. In cross sections, the Mmp20 (-/-) and Mmp20 (-/-) Klk4 (-/-) exhibited three distinct layers. The outer layer exhibited a disturbed elemental composition and an irregular enamel surface covered with nodules. The Mmp20 null enamel was apparently unable to withstand the sheer forces associated with eruption and separated from dentin during development. Cells invaded the cracks and interposed between the dentin and enamel layers. MMP20 and KLK4 serve overlapping and complementary functions to harden enamel by removing protein, but MMP20 potentially serves multiple additional functions necessary for the adherence of enamel to dentin, the release of intercellular protein stores into the enamel matrix, the retreat of ameloblasts to facilitate thickening of the enamel layer, and the timely transition of ameloblasts to maturation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.