title: The survival role of peroxisome proliferator-activated receptor gamma induces odontoblast differentiation against oxidative stress in human dental pulp cells.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPARγ) has well-known anti-inflammatory action in human dental pulp cells (HDPCs). The purpose of this study was to investigate whether the anti-inflammatory action of PPARγ involves in cellular cytoprotection and supports odontoblast differentiation under oxidative stress in HDPCs.
  
  
  METHODS
  To simulate long-term oxidative stress, pulp cells were treated with 150 μmol hydrogen peroxide (H(2)O(2)) for 12 days. The replication deficiency adenovirus (adenovirus PPARγ) was introduced for PPARγ overexpression in pulp cells. The cellular cytotoxicity and reactive oxygen species formation by H(2)O(2) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 2',7'-dichlorodihydrofluorescein diacetate with fluorescence-activated cell sorting assay. To determine the roles of PPARγ, several molecules of odontogenic/osteogenic and signal pathway were analyzed by reverse-transcription polymerase chain reaction and Western hybridization. Dentin mineralization was determined by alizarin red stain and alkaline phosphatase activity assay.
  
  
  RESULTS
  Pulp cells treated with long-term H(2)O(2) showed high reactive oxygen species formation, low cell viability, down-expression of antioxidant molecules (Cu/Zn and Mn superoxide dismutase), and odontogenic/osteogenic markers (eg, dentin sialophosphoprotein, dentin matrix protein-1, osteopontin, bone sialoprotein, Runx-2, and bone morphogenetic protein 2 and 7). In addition, pulp cells with oxidative stress underwent the activation of ERK1/2, activator protein-1, and nuclear factor-κB translocation to the nucleus. However, the PPARγ-overexpressed cells gave opposite results although under oxidative stress. Furthermore, PPARγ and its agonist rosiglitazone exhibited an induction of dentin mineralization under oxidative stress.
  
  
  CONCLUSIONS
  PPARγ in pulp cells increases cell viability, odontoblastic differentiation, and dentin mineralization under oxidative stress. These results offer new insights into the potential antioxidative activity of PPARγ and its agonist for therapeutic agents for pulp vitality in HDPCs.
authors: Department of Oral Biochemistry, Institute of Oral Bioscience, BK21 Program, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors: Young-Hee
authors: YH
authors: Lee
authors: Yu-Mi
authors: YM
authors: Kang
authors: Mi-Ja
authors: MJ
authors: Heo
authors: Go-Eun
authors: GE
authors: Kim
authors: Govinda
authors: G
authors: Bhattarai
authors: Nan-Hee
authors: NH
authors: Lee
authors: Mi-Kyung
authors: MK
authors: Yu
authors: Ho-Keun
authors: HK
authors: Yi
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D000880:Anthraquinones; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D019610:Cytoprotection / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D003804:Dentin / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D005456:Fluorescent Dyes; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000032:analysis; D009804:Odontoblasts / Q000187:drug effects*; D009805:Odontogenesis / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D016877:Oxidants / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013997:Time Factors; D014074:Tooth Calcification / Q000187:drug effects
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D004396:Coloring Agents; D005456:Fluorescent Dyes; D016328:NF-kappa B; D016877:Oxidants; D047495:PPAR gamma; D017382:Reactive Oxygen Species; C010078:alizarin; D006861:Hydrogen Peroxide; D000469:Alkaline Phosphatase