title: F-spondin negatively regulates dental follicle differentiation through the inhibition of TGF-β activity.
abstract: OBJECTIVE
  F-spondin is an extracellular matrix (ECM) protein that belongs to the thrombospondin type I repeat superfamily and is a negative regulator of bone mass. We have previously shown that f-spondin is specifically expressed in the dental follicle (DF), which gives rise to the periodontal ligament (PDL) during the tooth root formation stage. To investigate the molecular mechanism of PDL formation, we investigated the function of f-spondin in DF differentiation.
  
  
  METHODS
  The expression patterning of f-spondin in the developing tooth germ was compared with that of periodontal ligament-related genes, including runx2, type I collagen and periostin, by in situ hybridization analysis. To investigate the function of f-spondin during periodontal ligament formation, an f-spondin adenovirus was infected into the bell stage of the developing tooth germ, and the effect on dental differentiation was analyzed.
  
  
  RESULTS
  F-spondin was specifically expressed in the DF of the developing tooth germ; by contrast, type I collagen, runx2 and periostin were expressed in the DF and in the alveolar bone. F-spondin-overexpresssing tooth germ exhibited a reduction in gene expression of periostin and type I collagen in the DF. By contrast, the knockdown of f-spondin in primary DF cells increased the expression of these genes. Treatment with recombinant f-spondin protein functionally inhibited periostin expression induced by transforming growth factor-β (TGF-β).
  
  
  CONCLUSIONS
  Our data indicated that f-spondin inhibits the differentiation of DF cells into periodontal ligament cells by inhibiting TGF-β. These data suggested that f-spondin negatively regulates PDL differentiation which may play an important role in the immature phenotype of DF.
authors.affiliation: Division of Operative Dentistry, Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Orimoto
authors.affiliation: Faculty of Industrial Science and Technology, Tokyo University of Science, Katsushika, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Kurokawa
authors.affiliation: Division of Operative Dentistry, Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Handa
authors.affiliation: Division of Operative Dentistry, Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi-gakuin University, Nagoya, Aichi, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Nishida
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi-gakuin University, Nagoya, Aichi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Aino
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi-gakuin University, Nagoya, Aichi, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Mitani
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Division of Operative Dentistry, Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan. Electronic address: mssaito@dent.tohoku.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Saito
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003795:Dental Sac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D017403:In Situ Hybridization; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008810:Mice, Inbred C57BL; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D011994:Recombinant Proteins; D014083:Tooth Germ / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014092:Tooth Root / Q000254:growth & development / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; C552523:F-spondin protein, mouse; C082838:Postn protein, mouse; D011994:Recombinant Proteins; C493716:Runx2 protein, mouse; D016212:Transforming Growth Factor beta
keywords: Dental follicle differentiation; F-spondin; Periodontal ligament; TGF-β