Dental malformations associated with biallelic MMP20 mutations
Abstract Background Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation‐type amelogenesis imperfecta (AI2A2; OMIM #6...
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doaj-89d3f87d0001415bb348c887bd7e7fc12020-11-25T04:03:34ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-08-0188n/an/a10.1002/mgg3.1307Dental malformations associated with biallelic MMP20 mutationsShih‐Kai Wang0Hong Zhang1Michael B. Chavez2Yuanyuan Hu3Figen Seymen4Mine Koruyucu5Yelda Kasimoglu6Connor D. Colvin7Tamara N. Kolli8Michelle H. Tan9Yin‐Lin Wang10Pei‐Ying Lu11Jung‐Wook Kim12Brian L. Foster13John D. Bartlett14James P. Simmer15Jan C.‐C. Hu16Department of Biologic and Materials Sciences University of Michigan School of Dentistry Ann Arbor MI USADepartment of Biologic and Materials Sciences University of Michigan School of Dentistry Ann Arbor MI USADivision of Biosciences College of Dentistry The Ohio State University Columbus OH USADepartment of Biologic and Materials Sciences University of Michigan School of Dentistry Ann Arbor MI USADepartment of Pedodontics Istanbul University Faculty of Dentistry Istanbul TurkeyDepartment of Pedodontics Istanbul University Faculty of Dentistry Istanbul TurkeyDepartment of Pedodontics Istanbul University Faculty of Dentistry Istanbul TurkeyDivision of Biosciences College of Dentistry The Ohio State University Columbus OH USADivision of Biosciences College of Dentistry The Ohio State University Columbus OH USADivision of Biosciences College of Dentistry The Ohio State University Columbus OH USADepartment of Pediatric Dentistry National Taiwan University School of Dentistry Taipei City Taiwan R.O.C.Department of Pediatric Dentistry National Taiwan University School of Dentistry Taipei City Taiwan R.O.C.Department of Pediatric Dentistry & Dental Research Institute School of Dentistry Seoul National University Seoul Republic of KoreaDivision of Biosciences College of Dentistry The Ohio State University Columbus OH USADivision of Biosciences College of Dentistry The Ohio State University Columbus OH USADepartment of Biologic and Materials Sciences University of Michigan School of Dentistry Ann Arbor MI USADepartment of Biologic and Materials Sciences University of Michigan School of Dentistry Ann Arbor MI USAAbstract Background Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation‐type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear. Methods We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20−/− mice by histology, Backscattered Scanning Electron Microscopy (bSEM), µCT, and nanohardness testing. Results We identified six novel MMP20 disease‐causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin‐like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and µCT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%–69% of control. Characterization of Mmp20−/− mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization. Conclusion These results expand the spectrum of MMP20 disease‐causing mutations and provide the first evidence for MMP20 function during dentin formation.https://doi.org/10.1002/mgg3.1307amelogenesis imperfectaenamel hardnessdentin defectshypomineralizationMMP20 mutations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shih‐Kai Wang Hong Zhang Michael B. Chavez Yuanyuan Hu Figen Seymen Mine Koruyucu Yelda Kasimoglu Connor D. Colvin Tamara N. Kolli Michelle H. Tan Yin‐Lin Wang Pei‐Ying Lu Jung‐Wook Kim Brian L. Foster John D. Bartlett James P. Simmer Jan C.‐C. Hu |
spellingShingle |
Shih‐Kai Wang Hong Zhang Michael B. Chavez Yuanyuan Hu Figen Seymen Mine Koruyucu Yelda Kasimoglu Connor D. Colvin Tamara N. Kolli Michelle H. Tan Yin‐Lin Wang Pei‐Ying Lu Jung‐Wook Kim Brian L. Foster John D. Bartlett James P. Simmer Jan C.‐C. Hu Dental malformations associated with biallelic MMP20 mutations Molecular Genetics & Genomic Medicine amelogenesis imperfecta enamel hardness dentin defects hypomineralization MMP20 mutations |
author_facet |
Shih‐Kai Wang Hong Zhang Michael B. Chavez Yuanyuan Hu Figen Seymen Mine Koruyucu Yelda Kasimoglu Connor D. Colvin Tamara N. Kolli Michelle H. Tan Yin‐Lin Wang Pei‐Ying Lu Jung‐Wook Kim Brian L. Foster John D. Bartlett James P. Simmer Jan C.‐C. Hu |
author_sort |
Shih‐Kai Wang |
title |
Dental malformations associated with biallelic MMP20 mutations |
title_short |
Dental malformations associated with biallelic MMP20 mutations |
title_full |
Dental malformations associated with biallelic MMP20 mutations |
title_fullStr |
Dental malformations associated with biallelic MMP20 mutations |
title_full_unstemmed |
Dental malformations associated with biallelic MMP20 mutations |
title_sort |
dental malformations associated with biallelic mmp20 mutations |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2020-08-01 |
description |
Abstract Background Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation‐type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear. Methods We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20−/− mice by histology, Backscattered Scanning Electron Microscopy (bSEM), µCT, and nanohardness testing. Results We identified six novel MMP20 disease‐causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin‐like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and µCT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%–69% of control. Characterization of Mmp20−/− mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization. Conclusion These results expand the spectrum of MMP20 disease‐causing mutations and provide the first evidence for MMP20 function during dentin formation. |
topic |
amelogenesis imperfecta enamel hardness dentin defects hypomineralization MMP20 mutations |
url |
https://doi.org/10.1002/mgg3.1307 |
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