title: Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals.
abstract: Reconstruction of enamel-like materials is a central topic of research in dentistry and material sciences. The importance of precise proteolytic mechanisms in amelogenesis to form a hard tissue with more than 95% mineral content has already been reported. A mutation in the Matrix Metalloproteinase-20 (MMP-20) gene results in hypomineralized enamel that is thin, disorganized and breaks from the underlying dentin. We hypothesized that the absence of MMP-20 during amelogenesis results in the occlusion of amelogenin in the enamel hydroxyapatite crystals. We used spectroscopy and electron microscopy techniques to qualitatively and quantitatively analyze occluded proteins within the isolated enamel crystals from MMP-20 null and Wild type (WT) mice. Our results showed that the isolated enamel crystals of MMP-20 null mice had more organic macromolecules occluded inside them than enamel crystals from the WT. The crystal lattice arrangements of MMP-20 null enamel crystals analyzed by High Resolution Transmission Electron Microscopy (HRTEM) were found to be significantly different from those of the WT. Raman studies indicated that the crystallinity of the MMP-20 null enamel crystals was lower than that of the WT. In conclusion, we present a novel functional mechanism of MMP-20, specifically prevention of unwanted organic material entrapped in the forming enamel crystals, which occurs as the result of precise amelogenin cleavage. MMP-20 action guides the growth morphology of the forming hydroxyapatite crystals and enhances their crystallinity. Elucidating such molecular mechanisms can be applied in the design of novel biomaterials for future clinical applications in dental restoration or repair.
authors.affiliation: University of Southern California, Herman Ostrow School of Dentistry, Division of Biomedical Sciences, Center for Craniofacial Molecular Biology, Los Angeles, CA 90033, USA.
authors.forename: Saumya
authors.initials: S
authors.lastname: Prajapati
authors.affiliation: Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Tao
authors.affiliation: University of Southern California, Herman Ostrow School of Dentistry, Division of Biomedical Sciences, Center for Craniofacial Molecular Biology, Los Angeles, CA 90033, USA.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Ruan
authors.affiliation: Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: De Yoreo
authors.affiliation: University of Southern California, Herman Ostrow School of Dentistry, Division of Biomedical Sciences, Center for Craniofacial Molecular Biology, Los Angeles, CA 90033, USA. Electronic address: joldak@usc.edu.
authors.forename: Janet
authors.initials: J
authors.lastname: Moradian-Oldak
mesh_terms: D000818:Animals; D001031:Apatites / Q000378:metabolism*; D003460:Crystallization; D003743:Dental Enamel / Q000378:metabolism* / Q000648:ultrastructure; D053519:Matrix Metalloproteinase 20 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018625:Microscopy, Atomic Force; D008903:Minerals / Q000378:metabolism*; D013059:Spectrum Analysis, Raman
chemical_list: D001031:Apatites; D008903:Minerals; D053519:Matrix Metalloproteinase 20; C507113:Mmp20 protein, mouse
keywords: Amelogenin; Enamel biomineralization; Matrix metalloproteinase-20; Protein occlusion