title: Hertwig's epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by TGF-β.
abstract: In tooth root development, periodontal ligament (PDL) and cementum are formed by the coordination with the fragmentation of Hertwig's epithelial root sheath (HERS) and the differentiation of dental follicle mesenchymal cells. However, the function of the dental epithelial cells after HERS fragmentation in the PDL is not fully understood. Here, we found that TGF-β regulated HERS fragmentation via epithelial-mesenchymal transition (EMT), and the fragmented epithelial cells differentiated into PDL fibroblastic cells with expressing of PDL extracellular matrix (ECM). In the histochemical analysis, TGF-β was expressed in odontoblast layer adjacent of HERS during root development. Periostin expression was detected around fragmented epithelial cells on the root surface, but not in HERS. In the experiment using an established mouse HERS cell line (HERS01a), TGF-β1 treatment decreased E-cadherin and relatively increased N-cadherin expression. TGF-β1 treatment in HERS01a induced further expression of important ECM proteins for acellular cementum and PDL development such as fibronectin and periostin. Taken together, activation of TGF-βsignaling induces HERS fragmentation through EMT and the fragmented HERS cells contribute to formation of PDL and acellular cementum through periostin and fibronectin expression.
authors.affiliation: Section of Pediatric Dentistry, Department of Oral Growth and Development, Fukuoka Dental College.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itaya
authors.forename: Kyoko
authors.initials: K
authors.lastname: Oka
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogata
authors.forename: Shougo
authors.initials: S
authors.lastname: Tamura
authors.forename: Michiko
authors.initials: M
authors.lastname: Kira-Tatsuoka
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Keishi
authors.initials: K
authors.lastname: Otsu
authors.forename: Eichi
authors.initials: E
authors.lastname: Tsuruga
authors.forename: Masao
authors.initials: M
authors.lastname: Ozaki
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Harada
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003739:Dental Cementum / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D009804:Odontoblasts / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology*; D000076182:Sp7 Transcription Factor; D014092:Tooth Root / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D005353:Fibronectins; C082838:Postn protein, mouse; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D000469:Alkaline Phosphatase