title: Rat Notochordal Cells Undergo Premature Stress-Induced Senescence by High Glucose.
abstract: METHODS
  In vitro cell culture.
  
  
  OBJECTIVE
  The purpose of the study was to investigate the effect of high glucose on premature stress-induced senescence of rat notochordal cells.
  
  
  BACKGROUND
  Glucose-mediated increase of oxidative stress is a major causative factor for the development of diseases associated with diabetes mellitus such as senescence. However, no information is available for the effect of high glucose on premature stress-induced senescence of rat notochordal cells.
  
  
  METHODS
  Notochordal cells were isolated from 4-week-old rats, cultured and placed in either 10% fetal bovine serum (FBS, normal control) or 10% FBS plus two high glucose concentrations (0.1 M and 0.2 M, experimental conditions) for 1 and 3 days. We identified and quantified the mitochondrial damage (mitochondrial transmembrane potential), reactive oxygen species (ROS) and antioxidants, such as manganese superoxide dismutase (MnSOD) and catalase, for each condition. We also identified and quantified senescence and telomerase activity. Finally, we determined the expression of proteins related to replicative senescence (p53-p21-pRB) and stress-induced senescence (p16-pRB) pathways.
  
  
  RESULTS
  Two high glucose concentrations enhanced the disruption of mitochondrial transmembrane potential and excessive generation of ROS in notochordal cells for 1 and 3 days, respectively. The expressions of MnSOD and catalase were increased in notochordal cells treated with both high glucose concentrations at 1 and 3 days. The telomerase activity declined at 1 and 3 days. Two high glucose concentrations increased the occurrence of stress-induced senescence of notochordal cells by p16-pRB pathways at 1 and 3 days.
  
  
  CONCLUSIONS
  Despite compensatory expression of antioxidants, high glucose-induced oxidative stress accelerates stress-induced senescence in rat notochordal cells. This may result in dysfunction of notochordal cells, leading to accelerated premature disc degeneration. The prevention of excessive generation of oxidative stress by strict blood glucose control is important to prevent or to delay premature disc degeneration in young patients with diabetes mellitus.
authors.affiliation: Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Jong-Beom
authors.initials: JB
authors.lastname: Park
authors.affiliation: Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Chu-Hwan
authors.initials: CH
authors.lastname: Byun
authors.affiliation: Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Park
keywords: High glucose; Intervertebral disc degeneration; Notochordal cells; Stress-induced senescence