title: Senescence of nucleus pulposus chondrocytes in human intervertebral discs.
abstract: METHODS
  Senescence-related markers were assessed in surgically obtained human nucleus pulposus (NP) specimens.
  
  
  OBJECTIVE
  To demonstrate the mechanism and signaling pathway involved in the senescence of NP chondrocytes.
  
  
  BACKGROUND
  The population of senescent disc cells has been shown to be increased in degenerated or herniated discs. However, the mechanism and signaling pathway involved in the senescence of NP chondrocytes are unknown.
  
  
  METHODS
  We examined cell senescence markers [senescence-associated beta-galactosidase (SA-beta-gal), telomere length, telomerase activity, p53, p21, pRB and p16] and the hydrogen peroxide (H(2)O(2)) content in human NP specimens.
  
  
  RESULTS
  The percentage of SA-beta-gal-positive NP chondrocytes increased with age, while the telomere length and telomerase activity declined. However, there was no significant correlation between age and H(2)O(2) content. The NP specimens with grade III or IV degeneration showed significantly higher percentages of SA-beta-gal-positive NP chondrocytes than those with grade II degeneration. Immunohistochemistry showed that senescent NP chondrocytes in all specimens expressed p53, p21, and pRB, while a few NP chondrocytes in only two specimens expressed p16.
  
  
  CONCLUSIONS
  The present study demonstrates that, with increasing age and advancing disc degeneration, senescent NP chondrocytes increase or accumulate in the NP. Furthermore, the telomere-based p53, p21, pRB pathway, rather than the stress-based p16, pRB pathway, plays a more important role in the senescence of NP chondrocytes in in vivo conditions. Our results suggest that prevention or reversal of senescence of NP chondrocytes can be a novel mechanism by which to prevent human disc degeneration.
authors.affiliation: Department of Orthopedic Surgery, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ki-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Kee-Yong
authors.initials: KY
authors.lastname: Ha
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Na
authors.forename: Young-Yul
authors.initials: YY
authors.lastname: Kim
authors.forename: Young-Kyun
authors.initials: YK
authors.lastname: Woo
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