Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs

• Published in: The spine journal 2009-08, Vol.9 (8), p.658-666
• Main Authors: Kim, Ki-Won, MD, Chung, Ha-Na, BS, Ha, Kee-Yong, MD, Lee, Jun-Seok, MD, Kim, Young-Yul, MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; beta-Galactosidase - metabolism; Blotting, Western; Cells, Cultured; Cellular Senescence - physiology; Chondrocytes; Chondrocytes - metabolism; Chondrocytes - pathology; Disc degeneration; Female; Humans; Hydrogen Peroxide - metabolism; Immunohistochemistry; Intervertebral disc; Intervertebral Disc - metabolism; Intervertebral Disc - pathology; Intervertebral Disc Displacement - metabolism; Intervertebral Disc Displacement - pathology; Male; Middle Aged; Nucleus pulposus; Orthopedics; Senescence; Telomerase - metabolism; Telomere - metabolism; Telomere - pathology
• ISSN: 1529-9430; 1878-1632
• DOI: 10.1016/j.spinee.2009.04.018

Abstract Background context The population of senescent disc cells has been shown to increase in degenerated or herniated discs. However, the mechanism and signaling pathway involved in the senescence of nucleus pulposus (NP) chondrocytes are unknown. Purpose To demonstrate the mechanisms involved in the senescence of NP chondrocytes. Study design/setting Senescence-related markers were assessed in the surgically obtained human NP specimens. Patient sample NP specimens remaining in the central region of the intervertebral disc were obtained from 25 patients (mean: 49 years, range: 20–75 years) undergoing discectomy. Based on the preoperative magnetic resonance images, there were 3 patients with Grade II degeneration, 17 patients with Grade III degeneration, and 5 patients with Grade IV degeneration. Outcome measures We examined cell senescence markers (senescence-associated β-galactosidase [SA-β-gal], telomere length, telomerase activity, p53, p21, pRB, and p16) and the hydrogen peroxide (H2 O2 ) content as a marker for an oxidative stress in the human NP specimens. Methods SA-β-gal expression, telomere length, telomerase activity, and H2 O2 content as well as their relationships with age and degeneration grades were analyzed. For the mechanism involved in the senescence of NP chondrocytes, expressions of p53, p21, pRB, and p16 in these cells were assessed with immunohistochemistry and Western blotting. Results The percentages of SA-β-gal-positive NP chondrocytes increased with age (r=.82, p