title: Hepatocyte growth factor stimulates root growth during the development of mouse molar teeth.
abstract: OBJECTIVE
  It is well known that tooth root formation is initiated by the development of Hertwig's epithelial root sheath (HERS). However, relatively little is known about the regulatory mechanisms involved in root development. As hepatocyte growth factor (HGF) is one of the mediators of epithelial-mesenchymal interactions in rodent tooth, the objective of this study was to examine the effects of HGF on the root development of mouse molars.
  
  
  METHODS
  The HERS of mouse molars and HERS01a, a cell line originated from HERS, were used in this study. For detection of HGF receptors in vivo and in vitro, we used immunochemical procedures. Root development was assessed by implanting molar tooth germs along with HGF-soaked beads into kidney capsules, by counting cell numbers in HERS01a cell cultures and by performing a 5'-bromo-2'-deoxyuridine (BrdU) assay in an organ-culture system.
  
  
  RESULTS
  HGF receptors were expressed in the enamel epithelium of molar germs as well as in HERS cells. HGF stimulated root development in the transplanted tooth germs, the proliferation of HERS01a cells in culture and HERS elongation in the organ-culture system. Examination using BrdU revealed that cell proliferation in HERS was increased by treatment with HGF, especially that in the outer layer of HERS. This effect was down-regulated when antibody against HGF receptor was present in the culture medium.
  
  
  CONCLUSIONS
  Our results raise the possibility that HGF signaling controls root formation via the development of HERS. This study is the first to show that HGF is one of the stimulators of root development.
authors.affiliation: Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University, Morioka, Iwate, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
authors.forename: N
authors.initials: N
authors.lastname: Fujiwara
authors.forename: A
authors.initials: A
authors.lastname: Sasaki-Oikawa
authors.forename: M
authors.initials: M
authors.lastname: Sakano
authors.forename: Y
authors.initials: Y
authors.lastname: Tabata
authors.forename: K
authors.initials: K
authors.lastname: Otsu
authors.forename: K
authors.initials: K
authors.lastname: Ishizeki
authors.forename: H
authors.initials: H
authors.lastname: Harada
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002452:Cell Count; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003739:Dental Cementum / Q000166:cytology / Q000187:drug effects; D003804:Dentin / Q000166:cytology / Q000187:drug effects; D004658:Enamel Organ / Q000166:cytology / Q000254:growth & development; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008963:Molar / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D009805:Odontogenesis / Q000187:drug effects*; D009924:Organ Culture Techniques; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D019227:Tooth Apex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D014083:Tooth Germ / Q000166:cytology / Q000254:growth & development; D014092:Tooth Root / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*
chemical_list: D000963:Antimetabolites; C553307:HGF protein, mouse; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D001973:Bromodeoxyuridine