title: Effects of bioactive cements incorporating zinc-bioglass nanoparticles on odontogenic and angiogenic potential of human dental pulp cells.
abstract: BACKGROUND
  The objective of this study was to investigate the effects of bioactive calcium phosphate cements (CPC, α-tricalcium phosphate-based) incorporating zinc-bioglass (ZnBG) on the odontogenic differentiation and angiogenesis of human dental pulp cells (HDPCs).
  
  
  METHODS
  BGs with varying concentrations of Zn (0, 2.5 and 5%) were produced via a sol-gel process. The proliferation of HDPCs on CPC/BGs was determined by MTS assay. Alizarin red staining, RT-PCR, and ALP activity were used to assess odontogenic differentiation, and western blot analysis was used to asses signaling pathways. In vitro angiogenesis was examined via mRNA expression of angiogenic genes and tubule formation.
  
  
  RESULTS
  All cement formulations showed no cytotoxicity. The CPCs with ZnBG showed increased ALP activity, enhanced formation of mineralized nodules, and upregulated mRNA expression of DMP-1, DSPP, Runx2, and osterix in a time- and dose-dependent manner, relative to CPCs without Zn. ZnBG upregulated integrins α1, α2, β1, and β3 and activated integrin downstream signal pathways, such as p-FAK, p-Akt, p-paxillin, RhoA, MAPK, and NF-κB, as well as canonical and non-canonical Wnt signaling. In addition, ZnBG upregulated VEGF mRNA in HDPCs and increased the tubular structure in endothelial cells.
  
  
  CONCLUSIONS
  Our results demonstrate that ZnBG incorporated within CPCs activates odontogenic differentiation and promotes angiogenesis in vitro through integrin, Wnt, MAPK, and NF-κB pathways. Thus, CPCs incorporating ZnBG are promising matrices in tissue engineering to stimulate endodontic regeneration.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Preventive and Society Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yong-Duk
authors.initials: YD
authors.lastname: Park
authors.affiliation: Department of Maxillofacial Tissue Regeneration, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Bae
authors.affiliation: College of Dentistry & Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Fiqi
authors.affiliation: College of Dentistry & Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
authors.forename: Song-Hee
authors.initials: SH
authors.lastname: Shin
authors.affiliation: College of Dentistry & Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: College of Dentistry & Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea kimhw@dku.edu.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Maxillofacial Tissue Regeneration, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea eckim@khu.ac.kr.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D002130:Calcium Phosphates; D002454:Cell Differentiation; D002478:Cells, Cultured; D002516:Ceramics; D003738:Dental Cements / Q000737:chemistry; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000235:genetics; D009805:Odontogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015032:Zinc
chemical_list: C022107:Bioglass; D002130:Calcium Phosphates; D003738:Dental Cements; D012333:RNA, Messenger; D015032:Zinc
keywords: Zinc-bioglass nanoparticles; angiogenesis; dental pulp cells; odontogenic differentiation; tissue engineering