title: Interactions of enamel matrix derivative and biomechanical loading in periodontal regenerative healing.
abstract: BACKGROUND
  Although enamel matrix derivative (EMD) has been shown to promote periodontal regeneration, it is unknown whether the actions of EMD are modulated by occlusal loading. This in vitro study was performed to investigate whether biomechanical forces regulate the response of periodontal ligament (PDL) cells to EMD.
  
  
  METHODS
  Human PDL cells were treated with EMD in the presence and absence of cyclic tensile strain (CTS) of various magnitudes for ≤ 14 days. Synthesis of transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), growth factor receptors, collagen, and runt-related transcription factor 2- (RUNX2), cell numbers and adhesion, wound fill rate, and calcium accumulation were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, a wound healing assay, and alizarine red S staining.
  
  
  RESULTS
  Wound fill rate, cell numbers and adhesion, and expression of TGF-β1, VEGF, collagen, and RUNX2 were significantly increased by EMD. In the presence of CTS, the EMD-induced effects were significantly reduced. The inhibition of the EMD-upregulated VEGF expression by CTS was blocked by a specific inhibitor of nuclear factor-kappa B signaling. Moreover, CTS downregulated receptors for growth factors involved in the actions of EMD. CTS also antagonized significantly the EMD-induced calcium deposition.
  
  
  CONCLUSIONS
  These in vitro findings suggest that the beneficial actions of EMD on PDL cell functions critical for periodontal regeneration are jeopardized by biomechanical loading. Clinical studies should clarify whether protection of teeth against occlusal forces in the early healing stage may positively affect the outcome of regenerative therapy with EMD.
authors.affiliation: Clinical Research Unit 208, University of Bonn, Germany.
authors.forename: Marjan
authors.initials: M
authors.lastname: Nokhbehsaim
authors.forename: Birgit
authors.initials: B
authors.lastname: Deschner
authors.forename: Christoph
authors.initials: C
authors.lastname: Bourauel
authors.forename: Susanne
authors.initials: S
authors.lastname: Reimann
authors.forename: Jochen
authors.initials: J
authors.lastname: Winter
authors.forename: Björn
authors.initials: B
authors.lastname: Rath
authors.forename: Andreas
authors.initials: A
authors.lastname: Jäger
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.forename: James
authors.initials: J
authors.lastname: Deschner
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001696:Biomechanical Phenomena; D002113:Calcification, Physiologic; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D003799:Dental Stress Analysis; D005260:Female; D006801:Humans; D008297:Male; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013718:Tensile Strength; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D003746:Dental Enamel Proteins; C493709:RUNX2 protein, human; D017978:Receptors, Growth Factor; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C109069:enamel matrix proteins