title: Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress.
abstract: OBJECTIVE
  For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular response via loading-induced flow of interstitial fluid. After surgical removal of ectopically impacted third molars, human dental pulp tissue is an easily accessible and interesting source of cells for mineralized tissue engineering. The aim of this study was to determine whether human dental pulp-derived cells (DPC) are responsive to mechanical loading by pulsating fluid flow (PFF) upon stimulation of mineralization in vitro.
  
  
  METHODS
  Human DPC were incubated with or without mineralization medium containing differentiation factors for 3 weeks. Cells were subjected to 1-h PFF (0.7 ± 0.3 Pa, 5 Hz) and the response was quantified by measuring nitric oxide (NO) and prostaglandin E₂ (PGE₂) production, and gene expression of cyclooxygenase (COX)-1 and COX-2.
  
  
  RESULTS
  We found that DPC are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. PFF stimulated NO and PGE₂ production, and up-regulated COX-2 but not COX-1 gene expression. In DPC cultured under mineralizing conditions, the PFF-induced NO, but not PGE₂, production was significantly enhanced.
  
  
  CONCLUSIONS
  These data suggest that human DPC, like osteogenic cells, acquire responsiveness to pulsating fluid shear stress in mineralizing conditions. Thus DPC might be able to perform bone-like functions during mineralized tissue remodeling in vivo, and therefore provide a promising new tool for mineralized tissue engineering to restore, for example, maxillofacial defects.
authors.affiliation: Department of Orthodontics, School of Dentistry, University of Aarhus, Aarhus, Denmark. dckraft@odont.au.dk
authors.forename: David Christian Evar
authors.initials: DC
authors.lastname: Kraft
authors.forename: Dorth Arenholt
authors.initials: DA
authors.lastname: Bindslev
authors.forename: Birte
authors.initials: B
authors.lastname: Melsen
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klein-Nulend
mesh_terms: D016723:Bone Remodeling; D001842:Bone and Bones; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D008964:Molar, Third; D009569:Nitric Oxide / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011458:Prostaglandins E / Q000378:metabolism; D011673:Pulsatile Flow; D033081:Shear Strength; D013314:Stress, Mechanical; D023822:Tissue Engineering
chemical_list: D011458:Prostaglandins E; D009569:Nitric Oxide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2