title: Combination of Mineral Trioxide Aggregate and Platelet-rich Fibrin Promotes the Odontoblastic Differentiation and Mineralization of Human Dental Pulp Cells via BMP/Smad Signaling Pathway.
abstract: BACKGROUND
  Recent reports have shown that the combined use of platelet-rich fibrin (PRF), an autologous fibrin matrix, and mineral trioxide aggregate (MTA) as root filling material is beneficial for the endodontic management of an open apex. However, the potential of the combination of MTA and PRF as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro has not yet been studied. The purpose of this study was to evaluate the effect of the combination of MTA and PRF on odontoblastic maturation in HDPCs.
  
  
  METHODS
  HDPCs extracted from third molars were directly cultured with MTA and PRF extract (PRFe). Odontoblastic differentiation of HDPCs was evaluated by measuring the alkaline phosphatase (ALP) activity, and the expression of odontogenesis-related genes was detected using reverse-transcription polymerase chain reaction or Western blot. Mineralization formation was assessed by alizarin red staining.
  
  
  RESULTS
  HDPCs treated with MTA and PRFe significantly up-regulated the expression of dentin sialoprotein and dentin matrix protein-1 and enhanced ALP activity and mineralization compared with those with MTA or PRFe treatment alone. In addition, the combination of MTA and PRFe induced the activation of bone morphogenic proteins (BMP)/Smad, whereas LDN193189, the bone morphogenic protein inhibitor, attenuated dentin sialophosphoprotein and dentin matrix protein-1 expression, ALP activity, and mineralization enhanced by MTA and PRFe treatment.
  
  
  CONCLUSIONS
  This study shows that the combination of MTA and PRF has a synergistic effect on the stimulation of odontoblastic differentiation of HDPCs via the modulation of the BMP/Smad signaling pathway.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea; Research Center for Biomineralization Disorder, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea.
authors.forename: Su-Mi
authors.initials: SM
authors.lastname: Woo
authors.affiliation: Department of Oral Physiology, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea; Research Center for Biomineralization Disorder, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea.
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Dental Education, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea.
authors.forename: Hae-Soon
authors.initials: HS
authors.lastname: Lim
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea.
authors.forename: Nam-Ki
authors.initials: NK
authors.lastname: Choi
authors.affiliation: Research Center for Biomineralization Disorder, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea; Department of Oral Anatomy, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea.
authors.forename: Sun-Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea. Electronic address: impedo@jnu.ac.kr.
authors.forename: Seon-Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, South Korea. Electronic address: jjy@jnu.ac.kr.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Jung
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D017607:Aluminum Compounds / Q000494:pharmacology*; D001792:Blood Platelets; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017610:Calcium Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005337:Fibrin / Q000494:pharmacology*; D006801:Humans; D009804:Odontoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010087:Oxides / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics; D012387:Root Canal Filling Materials / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D017640:Silicates / Q000494:pharmacology*; D051785:Smad Proteins / Q000378:metabolism*; D015854:Up-Regulation; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D017607:Aluminum Compounds; D019485:Bone Morphogenetic Proteins; D017610:Calcium Compounds; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D005337:Fibrin; D010087:Oxides; D010750:Phosphoproteins; D012387:Root Canal Filling Materials; D012795:Sialoglycoproteins; D017640:Silicates; D051785:Smad Proteins; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human; C086631:mineral trioxide aggregate
keywords: BMP/Smad signaling; human dental pulp cells; mineral trioxide aggregate; odontogenic differentiation; platelet-rich fibrin