title: Effects of resinous monomers on the odontogenic differentiation and mineralization potential of highly proliferative and clonogenic cultured apical papilla stem cells.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of resinous monomers on the odontogenic differentiation and mineralization potential of apical papilla stem cells (SCAP).
  
  
  METHODS
  Cultures were established from developing third molars of healthy donors aged 14-18 years-old and were extensively characterized for proliferation rate, colony forming unit efficiency and expression of stem cell markers (STRO-1, CD146, CD34, CD45, CD105, CD117-c-Kit, CD24, CD90, Nanog, Oct3/4), in order to select those with enhanced stem cell and odontogenic differentiation properties. SCAP enriched cultures were then induced for odontogenic differentiation in the continuous presence of low concentrations (0.05-0.5 mM) of the monomers 2-hydroxy-ethyl-methacrylate-HEMA and triethylene-glycol-dimethacrylate-TEGDMA for 3 weeks (long-term exposure). Additionally, the effects of a single exposure (72 h) to higher concentrations of HEMA (2 mM) and TEGDMA (1 mM) were evaluated.
  
  
  RESULTS
  The results showed that both types of monomer-exposure significantly delayed the odontogenic differentiation and mineralization processes of SCAP cells. A down-regulation followed by recovery in the expression of differentiation markers, including dentin sialophosphoprotein-DSPP, bone sialoprotein-BSP, osteocalcin-OCN and alkaline phosphatase-ALP was recorded. This was accompanied by reduction of the mineralized matrix produced by monomer-treated-compared to non-treated contol cultures. Furthermore, a concentration-dependence was observed for both monomers during long-term exposure, whereas the effects of HEMA were evident at much lower concentrations compared to TEGDMA.
  
  
  CONCLUSIONS
  These findings suggest that resinous monomers can delay the odontogenic differentiation of SCAP cells, potentially disturbing the physiological repair and/or developmental processes of human permanent teeth.
authors.affiliation: Department of Fixed Prosthesis & Implant Prosthodontics, School of Dentistry, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Bakopoulou
authors.forename: Gabriele
authors.initials: G
authors.lastname: Leyhausen
authors.forename: Joachim
authors.initials: J
authors.lastname: Volk
authors.forename: Petros
authors.initials: P
authors.lastname: Koidis
authors.forename: Werner
authors.initials: W
authors.lastname: Geurtsen
mesh_terms: D000293:Adolescent; D053687:Adult Stem Cells / Q000187:drug effects*; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000096:biosynthesis; D008689:Methacrylates / Q000633:toxicity*; D009805:Odontogenesis / Q000187:drug effects*; D015675:Osteocalcin / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis; D011092:Polyethylene Glycols / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000633:toxicity*; D012795:Sialoglycoproteins / Q000096:biosynthesis; D019227:Tooth Apex / Q000166:cytology* / Q000187:drug effects*; D014074:Tooth Calcification / Q000187:drug effects; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D016326:Extracellular Matrix Proteins; D058574:Integrin-Binding Sialoprotein; D008689:Methacrylates; D015675:Osteocalcin; D010750:Phosphoproteins; D011092:Polyethylene Glycols; D011109:Polymethacrylic Acids; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C020946:triethylene glycol dimethacrylate; C005044:hydroxyethyl methacrylate