title: Six1 is required for mouse dental follicle cell and human periodontal ligament-derived cell proliferation.
abstract: The periodontal ligament (PDL) is a connective tissue that attaches the tooth cementum to the alveolar bone and is derived from dental follicle cells (DFCs). The DFCs form fibroblasts, osteoblasts, cementoblasts, and PDL stem cells (PDLSCs). We previously reported homeobox transcription factor Six1 expression in mouse DFCs. However, the role of Six1 in periodontal tissue development is largely unknown. In this study, we analyzed SIX1 expression in mouse periodontal tissue cells during postnatal development and adulthood. We also addressed the role of SIX1 in mouse periodontium development and in human cultured PDL-derived cells (PDLCs). In mouse development, SIX1 production was abundant in DFCs and PDL cells by 2 weeks, but it was greatly diminished in the PDL at 4 weeks and in adults. Although the SIX1-positive cell distribution was sparse in the adult PDL, SIX1-positive cells were observed with low expression levels. We used 5-ethynyl-2'-deoxyuridine (EdU) for cell labeling to reveal numerous EdU/SIX1-double positive cells at 2 weeks; however, a few EdU-positive cells remained at 4 weeks. The proportion of DFCs that incorporated EdU was significantly lower in Six1-deficient mice compared with wild-type mice at E18.5. In human PDLCs, SIX1 was intensely expressed, and SIX1-knockdown using siRNA reduced proliferating PDLCs. Our results suggest that SIX1 is a key proliferation regulator in mouse DFCs and human PDLCs, which provides novel insight into Six family gene function in mammals.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.|Division of Biology, Center for Molecular Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yajima
authors.affiliation: Department of Oral and Maxillofacial Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003795:Dental Sac / Q000166:cytology / Q000254:growth & development*; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010513:Periodontal Ligament / Q000166:cytology / Q000254:growth & development*
chemical_list: D018398:Homeodomain Proteins; C099236:SIX1 protein, human; C490947:Six1 protein, mouse; C022811:edoxudin; D003857:Deoxyuridine
keywords: SIX1; cell proliferation; dental follicle cells; periodontal ligament stem cells; periodontal ligament-derived cells