title: Enamel matrix derivative: a review of cellular effects in vitro and a model of molecular arrangement and functioning.
abstract: BACKGROUND
  Enamel matrix derivative (EMD), the active component of Emdogain®, is a viable option in the treatment of periodontal disease owing to its ability to regenerate lost tissue. It is believed to mimic odontogenesis, though the details of its functioning remain the focus of current research.
  
  
  OBJECTIVE
  The aim of this article is to review all relevant literature reporting on the composition/characterization of EMD as well as the effects of EMD, and its components amelogenin and ameloblastin, on the behavior of various cell types in vitro. In this way, insight into the underlying mechanism of regeneration will be garnered and utilized to propose a model for the molecular arrangement and functioning of EMD.
  
  
  METHODS
  A review of in vitro studies of EMD, or components of EMD, was performed using key words "enamel matrix proteins" OR "EMD" OR "Emdogain" OR "amelogenin" OR "ameloblastin" OR "sheath proteins" AND "cells." Results of this analysis, together with current knowledge on the molecular composition of EMD and the structure and regulation of its components, are then used to present a model of EMD functioning.
  
  
  RESULTS
  Characterization of the molecular composition of EMD confirmed that amelogenin proteins, including their enzymatically cleaved and alternatively spliced fragments, dominate the protein complex (>90%). A small presence of ameloblastin has also been reported. Analysis of the effects of EMD indicated that gene expression, protein production, proliferation, and differentiation of various cell types are affected and often enhanced by EMD, particularly for periodontal ligament and osteoblastic cell types. EMD also stimulated angiogenesis. In contrast, EMD had a cytostatic effect on epithelial cells. Full-length amelogenin elicited similar effects to EMD, though to a lesser extent. Both the leucine-rich amelogenin peptide and the ameloblastin peptides demonstrated osteogenic effects. A model for molecular structure and functioning of EMD involving nanosphere formation, aggregation, and dissolution is presented.
  
  
  CONCLUSIONS
  EMD elicits a regenerative response in periodontal tissues that is only partly replicated by amelogenin or ameloblastin components. A synergistic effect among the various proteins and with the cells, as well as a temporal effect, may prove important aspects of the EMD response in vivo.
authors: ETH Zurich, Department of Materials, Zurich, Switzerland.
authors: H Michelle
authors: HM
authors: Grandin
authors: Anja C
authors: AC
authors: Gemperli
authors: Michel
authors: M
authors: Dard
mesh_terms: D053523:Amelogenin / Q000494:pharmacology; D000818:Animals; D002477:Cells / Q000187:drug effects* / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological
chemical_list: D053523:Amelogenin; D003746:Dental Enamel Proteins; C109069:enamel matrix proteins