title: Role of the P38 pathway in calcium silicate cement-induced cell viability and angiogenesis-related proteins of human dental pulp cell in vitro.
abstract: BACKGROUND
  This study investigated that calcium silicate (CS) cement may influence the behavior of human dental pulp cells (hDPCs) via mitogen-activated protein kinase pathway, in particular p38. We have addressed that Si ion released from CS cement can influence osmolarity in the medium, which may stimulate hDPC viability and induce angiogenesis-related proteins through stimulation of the nitric oxide synthase and nitric oxide secretion.
  
  
  METHODS
  The hDPCs was cultured with CS cement to angiogenesis. Then, cell viability, ion concentration, osmolality, nitric oxide secretion, the von Willebrand factor, and angiopoietin-1 protein expression were examined.
  
  
  RESULTS
  CS cement elicited a significant (P < .05) increase of 15%, 20%, and 19% in viability compared with control on days 1, 3, and 5 of cell seeding, respectively. The CS cement consumed calcium and phosphate ions and released more Si ions in medium. The CS significantly (P < .05) increased the osmolality to 303.52 ± 3.07, 315.03 ± 5.80, and 319.95 ± 4.68 mOsm/kg for 1, 3, and 5 days, respectively. P38 was activated through phosphorylation; the phosphorylation kinase was investigated in our cell system after culture with CS cement. Moreover, expression levels for angiopoietin-1 and von Willebrand factor in hDPCs on CS cement were higher than those of the CS + p38 inhibitor (SB203580) group (P < .05) at all of the analyzed time points.
  
  
  CONCLUSIONS
  This study showed that CS cement was able to activate the p38 pathway in hDPCs cultured in vitro. Moreover, Si was shown to increase osmolality required to facilitate the angiogenic differentiation of hDPCs via the p38 signaling pathway. When the p38 pathway was blocked by SB203580, the angiogenic-dependent protein secretion was decreased. These findings verified that the p38 pathway plays a key role in regulating the angiogenic behavior of hDPCs cultured on CS cement.
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Ming-Yung
authors.initials: MY
authors.lastname: Chou
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Chia-Tze
authors.initials: CT
authors.lastname: Kao
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Chi-Jr
authors.initials: CJ
authors.lastname: Hung
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Tsui-Hsien
authors.initials: TH
authors.lastname: Huang
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Institute of Oral Science, Chung Shan Medical University, Taichung City, Taiwan. Electronic address: eviltacasi@gmail.com.
authors.forename: Ming-You
authors.initials: MY
authors.lastname: Shie
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Buor-Chang
authors.initials: BC
authors.lastname: Wu
mesh_terms: D042501:Angiogenic Proteins / Q000032:analysis*; D042683:Angiopoietin-1 / Q000032:analysis; D002118:Calcium / Q000737:chemistry; D017610:Calcium Compounds / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000201:enzymology; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects; D009994:Osmolar Concentration; D010710:Phosphates / Q000737:chemistry; D011725:Pyridines / Q000494:pharmacology; D012823:Silicate Cement / Q000494:pharmacology*; D017640:Silicates / Q000737:chemistry / Q000494:pharmacology*; D012825:Silicon / Q000737:chemistry; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: C467630:ANGPT1 protein, human; D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D017610:Calcium Compounds; D016166:Free Radical Scavengers; D007093:Imidazoles; D010710:Phosphates; D011725:Pyridines; D017640:Silicates; D014841:von Willebrand Factor; D012823:Silicate Cement; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C031293:calcium silicate; D002118:Calcium; D012825:Silicon
keywords: Angiogenesis; calcium silicate cement; human dental pulp cell; osmolality; p38/MAPK