title: High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts.
abstract: BACKGROUND
  Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high-glucose medium as a model of DM.
  
  
  METHODS
  PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)-(κB signaling pathway. The involvement of NF-κB was investigated with a specific NF-κB inhibitor in PDLSCs under hyperglycemic conditions.
  
  
  RESULTS
  High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-κB activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment.
  
  
  CONCLUSIONS
  The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation.
authors.affiliation: Department of Periodontology, Osaka Dental University, Osaka, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Periodontology, Osaka Dental University, Osaka, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Taguchi
authors.affiliation: Department of Oral Pathology, Osaka Dental University.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Department of Periodontology, Osaka Dental University, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kimura
authors.affiliation: Department of Periodontology, Osaka Dental University, Osaka, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Yamawaki
authors.affiliation: Department of Periodontology, Osaka Dental University, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Department of Periodontology, Osaka Dental University, Osaka, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamauchi
authors.affiliation: Department of Oral Anatomy, Osaka Dental University.
authors.forename: Isao
authors.initials: I
authors.lastname: Tamura
authors.affiliation: Department of Oral Pathology, Osaka Dental University.
authors.forename: Akio
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Periodontology, Osaka Dental University, Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Umeda
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D005947:Glucose; D006801:Humans; D010006:Osteoblasts; D010513:Periodontal Ligament; D013234:Stem Cells
chemical_list: D005947:Glucose
keywords: Cell differentiation; diabetes; hyperglycemia; osteoblasts; periodontal ligament; stem cells