Yoshiko Masuda1, Hiroshi Sakagami2, Satoshi Yokose3, Nobuyuki Udagawa4. 1. Department of Operative Dentistry, Matsumoto Dental University, Nagano, Japan yoshiko.masuda@mdu.ac.jp. 2. Meikai University Research Institute of Odontology (M-RIO), Meikai University School of Dentistry, Saitama, Japan. 3. Division of Endodontics and Operative Dentistry, Meikai University School of Dentistry, Saitama, Japan. 4. Department of Biochemistry, Matsumoto Dental University, Nagano, Japan.
Abstract
BACKGROUND: It has been reported that glycogen synthase kinase 3 (GSK3) antagonist promoted the reparative formation of dentin. The aim of the present study was to evaluate whether treatment schedule of Tidegrusib® (TG), a small-molecule GSK3 antagonist, affected in vitro differentiation of dental pulp cells toward odontoblast-like cells. MATERIALS AND METHODS: Pulp cells isolated from rat incisors were repeatedly exposed to TG for the first 6 h (intermittent exposure) or the full 48 h (continuous exposure) of each 48-h incubation cycle. Histological analysis of alkaline phosphatase and von Kossa staining were performed. The expression of dentin sialophosphoprotein (Dspp) and osteocalcin (Ocn) mRNA were examined by real-time polymerase chain reaction. Western blotting assays were used to monitor the expression of β-catenin and its phosphorylated form. RESULTS: When pulp cells were intermittently exposed to TG for only the first 6 h of each incubation cycle, pulp cells differentiated into odontoblast-like cells, characterized by an increase in alkaline phosphatase activity, nodule formation, and mRNA expression of Dspp. and Ocn; this did not occur under the continuous exposure. Phosphorylation of β-catenin was enhanced by continuous exposure to TG compared with intermittent exposure. CONCLUSION: These results suggest that the TG-induced odontoblast-like cell differentiation reflects in vivo reparative dentin formation and depends on the exposure time. Copyright
BACKGROUND: It has been reported that glycogen synthase kinase 3 (GSK3) antagonist promoted the reparative formation of dentin. The aim of the present study was to evaluate whether treatment schedule of Tidegrusib® (TG), a small-molecule GSK3 antagonist, affected in vitro differentiation of dental pulp cells toward odontoblast-like cells. MATERIALS AND METHODS: Pulp cells isolated from rat incisors were repeatedly exposed to TG for the first 6 h (intermittent exposure) or the full 48 h (continuous exposure) of each 48-h incubation cycle. Histological analysis of alkaline phosphatase and von Kossa staining were performed. The expression of dentin sialophosphoprotein (Dspp) and osteocalcin (Ocn) mRNA were examined by real-time polymerase chain reaction. Western blotting assays were used to monitor the expression of β-catenin and its phosphorylated form. RESULTS: When pulp cells were intermittently exposed to TG for only the first 6 h of each incubation cycle, pulp cells differentiated into odontoblast-like cells, characterized by an increase in alkaline phosphatase activity, nodule formation, and mRNA expression of Dspp. and Ocn; this did not occur under the continuous exposure. Phosphorylation of β-catenin was enhanced by continuous exposure to TG compared with intermittent exposure. CONCLUSION: These results suggest that the TG-induced odontoblast-like cell differentiation reflects in vivo reparative dentin formation and depends on the exposure time. Copyright
Authors: Eduardo Tolosa; Irene Litvan; Günter U Höglinger; David Burn; Andrew Lees; María V Andrés; Belén Gómez-Carrillo; Teresa León; Teodoro Del Ser Journal: Mov Disord Date: 2014-02-14 Impact factor: 10.338