title: A New Calcium Silicate-based Bioceramic Material Promotes Human Osteo- and Odontogenic Stem Cell Proliferation and Survival via the Extracellular Signal-regulated Kinase Signaling Pathway.
abstract: BACKGROUND
  The purpose of this study was to investigate odontogenic and osteogenic cell adhesion, proliferation, and survival on the surface of a newly developed bioceramic material (EndoSequence Root Repair Material [RRM]; Brasseler USA, Savannah, GA) and compare it with mineral trioxide aggregate (gray MTA) (ProRoot MTA; Dentsply Tulsa Dental, Tulsa, OK). A potential role of extracellular signal-regulated kinase (ERK) signaling in the RRM/MTA-induced cellular activities was also investigated.
  
  
  METHODS
  Human bone marrow mesenchymal stem cells, periodontal ligament stem cells, and dental pulp stem cells were cultured on RRM- or MTA-coated slides. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays after 1, 3, and 5 days of growth. Cell survival was assessed under serum starvation (0.5% and 0.2% serum) using MTT assays. RRM and MTA surface characteristics and cell morphology were studied using a scanning electron microscope. The role of ERK signaling in RRM/MTA-induced cell proliferation/survival was studied using an ERK-specific inhibitor.
  
  
  RESULTS
  All cell types firmly attached to RRM- and MTA-coated plates. The coated surfaces had a granular appearance under the scanning electron microscope. Compared with those grown on uncoated plates, the cells on MTA/RRM-coated plates appeared healthy and smaller. Cell proliferation was significantly higher on RRM/MTA-coated surfaces (2- to 3-fold in cell number). The mitogenic effect on periodontal ligament stem cells and dental pulp stem cells was more pronounced with RRM than MTA (49% and 26% higher, respectively), but human bone marrow mesenchymal stem cells responded to both materials similarly. In serum-deprived conditions, significantly more cells (2- to 3-fold) survived on RRM/MTA surfaces. The cells grown on RRM/MTA surfaces showed sustained up-regulation of ERK phosphorylation, and blocking ERK signaling with U0126 significantly reduced RRM- and MTA-dependent cell survival.
  
  
  CONCLUSIONS
  MTA and RRM are biocompatible and promote cell proliferation and survival in an ERK-dependent manner.
authors.affiliation: Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ian
authors.initials: I
authors.lastname: Chen
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Imad
authors.initials: I
authors.lastname: Salhab
authors.affiliation: Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Setzer
authors.affiliation: Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Syngcuk
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address: nah@email.chop.edu.
authors.forename: Hyun-Duck
authors.initials: HD
authors.lastname: Nah
mesh_terms: D017607:Aluminum Compounds / Q000494:pharmacology; D017610:Calcium Compounds / Q000737:chemistry / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002516:Ceramics / Q000737:chemistry / Q000494:pharmacology*; D004338:Drug Combinations; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009805:Odontogenesis / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology; D012387:Root Canal Filling Materials / Q000494:pharmacology; D017640:Silicates / Q000737:chemistry / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*
chemical_list: D017607:Aluminum Compounds; D017610:Calcium Compounds; D002130:Calcium Phosphates; D004338:Drug Combinations; C550603:EndoSequence root repair material; D010087:Oxides; D012387:Root Canal Filling Materials; D017640:Silicates; C086631:mineral trioxide aggregate; D048049:Extracellular Signal-Regulated MAP Kinases; C031293:calcium silicate
keywords: Bioceramics; cell proliferation; cell survival; cytotoxicity; extracellular signal-regulated kinase signaling; mineral trioxide aggregate; root repair material