title: TGF-β1 and FGF2 stimulate the epithelial-mesenchymal transition of HERS cells through a MEK-dependent mechanism.
abstract: Hertwig's epithelial root sheath (HERS) cells participate in cementum formation through epithelial-mesenchymal transition (EMT). Previous studies have shown that transforming growth factor beta 1 (TGF-β1) and fibroblast growth factor 2 (FGF2) are involved in inducing EMT. However, their involvement in HERS cell transition remains elusive. In this study, we confirmed that HERS cells underwent EMT during the formation of acellular cementum. We found that both TGF-β1 and FGF2 stimulated the EMT of HERS cells. The TGF-β1 regulated the differentiation of HERS cells into periodontal ligament fibroblast-like cells, and FGF2 directed the differentiation of HERS cells into cementoblast-like cells. Treatment with TGF-β1 or FGF2 inhibitor could effectively suppress HERS cells differential transition. Combined stimulation with both TGF-β1 and FGF-2 did not synergistically accelerate the EMT of HERS. Moreover, TGF-β1/FGF2-mediated EMT of HERS cells was reversed by the MEK1/2 inhibitor U0126. These results suggest that TGF-β1 and FGF2 induce the EMT of HERS through a MAPK/ERK-dependent signaling pathway. They also exert their different tendency of cellular differentiation during tooth root formation. This study further expands our knowledge of tooth root morphogenesis and provides more evidence for the use of alternative cell sources in clinical treatment of periodontal diseases.
authors.affiliation: National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P.R. China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P.R. China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Yan
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Guo
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: Lian
authors.initials: L
authors.lastname: Feng
authors.forename: Zongting
authors.initials: Z
authors.lastname: Jiang
authors.forename: Weihua
authors.initials: W
authors.lastname: Guo
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003739:Dental Cementum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D016130:Immunophenotyping; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases