title: Effects of Adenosine Triphosphate on Proliferation and Odontoblastic Differentiation of Human Dental Pulp Cells.
abstract: BACKGROUND
  Adenosine 5'-triphosphate (ATP) is a potent signaling molecule that regulates diverse biological activities in cells. Its effects on human dental pulp cells (HDPCs) remain unknown. This study aimed to examine the effects of ATP on proliferation and differentiation of HDPCs.
  
  
  METHODS
  Reverse transcription polymerase chain reaction was performed to explore the mRNA expression of P2 receptor subtypes. Cell Counting Kit-8 test and flow cytometry analysis were used to examine the effects of ATP on proliferation and cell cycle of HDPCs. The effects of ATP on differentiation of HDPCs were examined by using alizarin red S staining, energy-dispersive x-ray analysis, Western blot analysis, and real-time polymerase chain reaction.
  
  
  RESULTS
  The purinoceptors P2X3, P2X4, P2X5, P2X7, and all P2Y receptor subtypes were confirmed to present in HDPCs. ATP enhanced HDPC proliferation at 10 μmol/L concentration. However, it inhibited cell proliferation by arresting the cell cycle in G0G1 phase (P < .05 versus control) and induced odontoblastic differentiation, ERK/MAPK activation, and dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) mRNA transcriptions at 800 μmol/L concentration. Suramin, an ATP receptor antagonist, inhibited ERK/MAPK activation and HDPC odontoblastic differentiation (P < .05 versus control).
  
  
  CONCLUSIONS
  Extracellular ATP activates P2 receptors and downstream signaling events that induce HDPC odontogenic differentiation. Thus, ATP may promote dental pulp tissue healing and repair through P2 signaling. Results provide new insights into the molecular regulation of pulpal wound healing.
authors: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China; Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China; Department of Stomatology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China; Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China.
authors: Xiaosong
authors: X
authors: Yi
authors: University of Rochester Eastman Institute for Oral Health, Rochester, New York.
authors: Yanfang
authors: Y
authors: Ren
authors: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China; Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China. Electronic address: xieqiuf@163.com.
authors: Qiufei
authors: Q
authors: Xie
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D002070:Butadienes / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D003810:Dentinogenesis / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009804:Odontoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D055815:Young Adult
chemical_list: D002070:Butadienes; D009570:Nitriles; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; C113580:U 0126; D013498:Suramin; D000255:Adenosine Triphosphate
keywords: Dentin matrix protein 1; ERK pathway; dentin sialophosphoprotein; dentinogenesis; odontoblast; purinergic P2 receptors