title: Combined effects of mineral trioxide aggregate and human placental extract on rat pulp tissue and growth, differentiation and angiogenesis in human dental pulp cells.
abstract: OBJECTIVE
  The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined.
  
  
  METHODS
  MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed.
  
  
  RESULTS
  Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-κB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-κB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics.
authors.affiliation: a Department of Conservative Dentistry ;
authors.forename: Seok-Woo
authors.initials: SW
authors.lastname: Chang
authors.affiliation: b Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC );
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: b Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC );
authors.forename: Mi-Joo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: b Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC );
authors.forename: Ga-Hyun
authors.initials: GH
authors.lastname: Kim
authors.affiliation: a Department of Conservative Dentistry ;
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Yi
authors.affiliation: c Department of Oral and Maxillofacial Surgery School of Dentistry , Kyung Hee University , Seoul , Republic of Korea ;
authors.forename: Deok-Won
authors.initials: DW
authors.lastname: Lee
authors.affiliation: d Department of Conservative Dentistry , Seoul National University Dental Hospital , Seoul , Republic of Korea.
authors.forename: Kee-Yeon
authors.initials: KY
authors.lastname: Kum
authors.affiliation: b Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC );
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects; D017607:Aluminum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D017610:Calcium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D002196:Capillaries / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D003809:Dentin, Secondary / Q000187:drug effects; D004338:Drug Combinations; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D010924:Placental Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D057872:Pulp Capping and Pulpectomy Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D017640:Silicates / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
chemical_list: D017607:Aluminum Compounds; D017610:Calcium Compounds; D004338:Drug Combinations; D016328:NF-kappa B; D010087:Oxides; D010924:Placental Extracts; D057872:Pulp Capping and Pulpectomy Agents; D017640:Silicates; C086631:mineral trioxide aggregate; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D000469:Alkaline Phosphatase
keywords: Angiogenesis; MTA; human dental pulp cells; human placental extract; odontogenic differentiation