title: Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products.
abstract: BACKGROUND
  Proangiogenic prolyl hydroxylase (PHD) inhibitors represent a novel approach to stimulate tissue regeneration. Diabetes mellitus involves the accumulation of advanced glycation end products (AGEs). Here we evaluated the impact of AGEs on the response of human pulp tissue to the PHD inhibitor L-mimosine (L-MIM) in monolayer cultures of dental pulp-derived cells (DPCs) and tooth slice organ cultures.
  
  
  METHODS
  In monolayer cultures, DPCs were incubated with L-MIM and AGEs. Viability was assessed based on formazan formation, live-dead staining, annexin V/propidium iodide, and trypan blue exclusion assay. Vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 production was evaluated by quantitative polymerase chain reaction and immunoassays. Furthermore, expression levels of odontoblast markers were assessed, and alizarin red staining was performed. Tooth slice organ cultures were performed, and VEGF, IL-6, and IL8 levels in their supernatants were measured by immunoassays. Pulp tissue vitality and morphology were assessed by MTT assay and histology.
  
  
  RESULTS
  In monolayer cultures of DPCs, L-MIM at nontoxic concentrations increased the production of VEGF and IL-8 in the presence of AGEs. Stimulation with L-MIM decreased alkaline phosphatase levels and matrix mineralization also in the presence of AGEs, whereas no significant changes in dentin matrix protein 1 and dentin sialophosphoprotein expression were observed. In tooth slice organ cultures, L-MIM increased VEGF but not IL-6 and IL-8 production in the presence of AGEs. The pulp tissue was vital, and no signs of apoptosis or necrosis were observed.
  
  
  CONCLUSIONS
  Overall, in the presence of AGEs, L-MIM increases the proangiogenic capacity, but decreases alkaline phosphatase expression and matrix mineralization.
authors.affiliation: Department of Prosthodontics, Medical University of Vienna, Vienna, Austria; Department of Preventive, Restorative and Pediatric Dentistry, University of Bern, Bern, Switzerland; Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Heinz-Dieter
authors.initials: HD
authors.lastname: Müller
authors.affiliation: Department of Preventive, Restorative and Pediatric Dentistry, University of Bern, Bern, Switzerland; Austrian Cluster for Tissue Regeneration, Vienna, Austria; Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cvikl
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria; Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria.
authors.forename: Klara
authors.initials: K
authors.lastname: Janjić
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria; Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria; Department of Trauma Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Nürnberger
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria; Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Moritz
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria; Department of Oral Biology, Medical University of Vienna, Vienna, Austria; Laboratory for Oral Cell Biology, University of Bern, Bern, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gruber
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria; Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria. Electronic address: hermann.agis@meduniwien.ac.at.
authors.forename: Hermann
authors.initials: H
authors.lastname: Agis
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003782:Dental Pulp / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D017127:Glycation End Products, Advanced; D006801:Humans; D007150:Immunohistochemistry; D008898:Mimosine / Q000378:metabolism*; D008954:Models, Biological; D009924:Organ Culture Techniques; D064800:Prolyl-Hydroxylase Inhibitors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017127:Glycation End Products, Advanced; D064800:Prolyl-Hydroxylase Inhibitors; D008898:Mimosine
keywords: Advanced glycation end product; dental pulp; diabetes; interleukin; pulp regeneration; tissue engineering; vascular endothelial growth factor