Table of Contents Author Guidelines Submit a Manuscript
ISRN Dentistry
Volume 2013 (2013), Article ID 684607, 24 pages
Review Article

Dental Enamel Development: Proteinases and Their Enamel Matrix Substrates

Harvard School of Dental Medicine & Chair, Department of Mineralized Tissue Biology, The Forsyth Institute, 245 First Street, Cambridge MA 02142, USA

Received 27 June 2013; Accepted 15 July 2013

Academic Editors: A. Jäger and J. H. Jeng

Copyright © 2013 John D. Bartlett. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


This review focuses on recent discoveries and delves in detail about what is known about each of the proteins (amelogenin, ameloblastin, and enamelin) and proteinases (matrix metalloproteinase-20 and kallikrein-related peptidase-4) that are secreted into the enamel matrix. After an overview of enamel development, this review focuses on these enamel proteins by describing their nomenclature, tissue expression, functions, proteinase activation, and proteinase substrate specificity. These proteins and their respective null mice and human mutations are also evaluated to shed light on the mechanisms that cause nonsyndromic enamel malformations termed amelogenesis imperfecta. Pertinent controversies are addressed. For example, do any of these proteins have a critical function in addition to their role in enamel development? Does amelogenin initiate crystallite growth, does it inhibit crystallite growth in width and thickness, or does it do neither? Detailed examination of the null mouse literature provides unmistakable clues and/or answers to these questions, and this data is thoroughly analyzed. Striking conclusions from this analysis reveal that widely held paradigms of enamel formation are inadequate. The final section of this review weaves the recent data into a plausible new mechanism by which these enamel matrix proteins support and promote enamel development.