title: TLR signalling can modify the mineralization of tooth germ.
abstract: OBJECTIVE
  The aim of this work is to investigate the possible role of Toll-like receptor 4 (TLR4) during the development of mouse tooth germ. TLR4 is well known to inhibit mineralization and cause inflammation in mature odontoblasts and dental pulp cells. However, unlike these pathological functions of TLR4, little is known about the developmental function(s) of TLR4 during tooth development.
  
  
  METHODS
  TLR4 expression was studied via Western blot in developing lower mouse incisors from E13.5 to E18.5. To generate functional data about the effects of TLR4, a specific agonist (LPS) was applied to the medium of in vitro tooth germ cultures, followed by Western blot, histochemical staining, ELISA assay, in situ hybridization and RT-qPCR.
  
  
  RESULTS
  Increased accumulation of biotin-labelled LPS was detected in the enamel organ and in preodontoblasts. LPS treatment induced degradation of the inhibitor molecule (IκB) of the NF-κB signalling pathway. However, no morphological alterations were detected in cultured tissue after LPS addition at the applied dosage. Activation of TLR4 inhibited the mineralization of enamel and dentin, as demonstrated by alizarin red staining and as decreased levels of collagen type X. mRNA expression of ameloblastin was elevated after LPS administration.
  
  
  CONCLUSIONS
  These results demonstrate that TLR4 may decrease the mineralization of hard tissues of the tooth germ and may trigger the maturation of ameloblasts; it can give valuable information to understand better congenital tooth abnormalities.
authors.affiliation: a Department of Anatomy, Histology and Embryology; Faculty of Medicine , University of Debrecen , Debrecen , Hungary ;
authors.forename: Tamas
authors.initials: T
authors.lastname: Papp
authors.affiliation: a Department of Anatomy, Histology and Embryology; Faculty of Medicine , University of Debrecen , Debrecen , Hungary ;
authors.forename: Krisztina
authors.initials: K
authors.lastname: Hollo
authors.affiliation: a Department of Anatomy, Histology and Embryology; Faculty of Medicine , University of Debrecen , Debrecen , Hungary ;
authors.forename: Eva
authors.initials: E
authors.lastname: Meszar-Katona
authors.affiliation: a Department of Anatomy, Histology and Embryology; Faculty of Medicine , University of Debrecen , Debrecen , Hungary ;
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Nagy
authors.affiliation: a Department of Anatomy, Histology and Embryology; Faculty of Medicine , University of Debrecen , Debrecen , Hungary ;
authors.forename: Angela
authors.initials: A
authors.lastname: Polyak
authors.affiliation: b Department of Medical Chemistry , University of Debrecen , Debrecen , Hungary ;|c MTA-DE Lendület Laboratory of Cellular Metabolism Research Group , Debrecen , Hungary ;|d Research Center for Molecular Medicine, University of Debrecen , Debrecen , Hungary ;
authors.forename: Edit
authors.initials: E
authors.lastname: Miko
authors.affiliation: b Department of Medical Chemistry , University of Debrecen , Debrecen , Hungary ;|c MTA-DE Lendület Laboratory of Cellular Metabolism Research Group , Debrecen , Hungary ;|d Research Center for Molecular Medicine, University of Debrecen , Debrecen , Hungary ;
authors.forename: Peter
authors.initials: P
authors.lastname: Bai
authors.affiliation: a Department of Anatomy, Histology and Embryology; Faculty of Medicine , University of Debrecen , Debrecen , Hungary ;|e Department of Oral Anatomy, Faculty of Dentistry , University of Debrecen , Debrecen , Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Felszeghy
mesh_terms: D000565:Ameloblasts / Q000187:drug effects; D000818:Animals; D024121:Collagen Type X / Q000032:analysis / Q000187:drug effects; D003743:Dental Enamel / Q000187:drug effects / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000032:analysis / Q000187:drug effects; D003804:Dentin / Q000187:drug effects / Q000378:metabolism; D004658:Enamel Organ / Q000187:drug effects / Q000378:metabolism; D020672:I-kappa B Proteins / Q000032:analysis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009804:Odontoblasts / Q000187:drug effects / Q000378:metabolism; D009805:Odontogenesis / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000502:physiology*; D014074:Tooth Calcification / Q000187:drug effects / Q000502:physiology*; D014083:Tooth Germ / Q000187:drug effects / Q000502:physiology*
chemical_list: C490890:Ambn protein, mouse; D024121:Collagen Type X; D003746:Dental Enamel Proteins; D020672:I-kappa B Proteins; C551354:IkappaBeta protein, mouse; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: LPS; development; enamel organ; incisor