%0 Journal Article
%T Dental Enamel Development: Proteinases and Their Enamel Matrix Substrates
%A John D. Bartlett
%J ISRN Dentistry
%D 2013
%R 10.1155/2013/684607
%X 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. 1. Introduction Tooth development is a highly orchestrated process that begins with the defined placement of individual teeth of specific shapes and sizes within the jaw. Precise signaling pathways to and from epithelial and mesenchymal cells are required for each tooth to initiate and continue along its developmental path [1, 2]. The complexity of these pathways is reflected by their high rate of incompletion. Deficiency of third molars, second premolars, and lateral incisors is common. The reported incidence of selective agenesis varies from 1.6% to 9.6% for all but third molars. Agenesis of third molars occurs in approximately 20% of the World¡¯s population [3]. Therefore, the study of tooth development has taught us how genes and tissues interact to form complex dental structures that each occupies a prespecified place within the jaw and has taught us about what can go wrong with the intricate developmental signaling pathways. Teeth are composed of three different mineralized tissues: cementum, dentin, and enamel. Cementum is found along the tooth root and primarily serves to hold the tooth in place by binding collagen fibers (Sharpey¡¯s fibers) that are continuous with the principal fibers of
%U http://www.hindawi.com/journals/isrn.dentistry/2013/684607/