title: Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells.
abstract: Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway.
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 Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Chen
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.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
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.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Sun
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 Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Li
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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
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 Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Xianrui
authors.initials: X
authors.lastname: Yang
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 Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
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.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
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 School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
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.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
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 Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Ding
authors.initials: D
authors.lastname: Bai
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D003771:Dental Papilla / Q000166:cytology*; D008954:Models, Biological; D009805:Odontogenesis / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014070:Tooth / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D016227:Benzoquinones; D011422:Propionates; D034741:RNA, Small Interfering; C075569:E 3330; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase