Hertwig’s epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by TGF-β

• Published in: Biomedical Research 2017/02/01, Vol.38(1), pp.61-69
• Main Authors: ITAYA, Satoshi, OKA, Kyoko, OGATA, Kayoko, TAMURA, Shougo, -TATSUOKA, Michiko KIRA, FUJIWARA, Naoki, OTSU, Keishi, TSURUGA, Eichi, OZAKI, Masao, HARADA, Hidemitsu
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Animals; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Differentiation - physiology; Cell Line; Cementum; Collagen Type I - genetics; Collagen Type I - metabolism; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Dental Cementum - cytology; E-cadherin; Epithelial cells; Epithelial Cells - cytology; Epithelial-Mesenchymal Transition - physiology; Extracellular matrix; Extracellular Matrix - metabolism; Fibronectin; Fibronectins - genetics; Fibronectins - metabolism; Gene Expression Regulation; Mesenchyme; Mice; N-Cadherin; Odontoblasts - cytology; Odontoblasts - metabolism; Osteocalcin - genetics; Osteocalcin - metabolism; Periodontal ligament; Periodontal Ligament - cytology; Proteins; Root development; Sp7 Transcription Factor; Teeth; Tooth Root - cytology; Transcription Factors - genetics; Transcription Factors - metabolism; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1
• ISSN: 0388-6107; 1880-313X
• DOI: 10.2220/biomedres.38.61

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.