Anatomy and Cell Biology

  • 제56권3호
  • /
  • Pages.382-393
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  • 2023
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  • 2093-3665(pISSN)
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  • 2093-3673(eISSN)
대한해부학회 (Korean Association of Anatomists)
권호 표지
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Cell clusters in intervertebral disc degeneration: an attempted repair mechanism aborted via apoptosis

  • Polly Lama (Department of Anatomy, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University) ;
  • Jerina Tiwari (Department of Anatomy, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University) ;
  • Pulkit Mutreja (Department of Anatomy, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University) ;
  • Sukirti Chauhan (Department of Anatomy, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University) ;
  • Ian J Harding (Centre for Clinical Anatomy, University of Bristol) ;
  • Trish Dolan (Centre for Clinical Anatomy, University of Bristol) ;
  • Michael A Adams (Centre for Clinical Anatomy, University of Bristol) ;
  • Christine Le Maitre (Biomolecular Research Centre, Sheffield Hallam University)
  • 투고 : 2023.03.08
  • 심사 : 2023.05.22
  • 발행 : 2023.09.30
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초록

Cell clusters are a histological hallmark feature of intervertebral disc degeneration. Clusters arise from cell proliferation, are associated with replicative senescence, and remain metabolically, but their precise role in various stages of disc degeneration remain obscure. The aim of this study was therefore to investigate small, medium, and large size cell-clusters. For this purpose, human disc samples were collected from 55 subjects, aged 37-72 years, 21 patients had disc herniation, 10 had degenerated non-herniated discs, and 9 had degenerative scoliosis with spinal curvature <45°. 15 non-degenerated control discs were from cadavers. Clusters and matrix changes were investigated with histology, immunohistochemistry, and Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Data obtained were analyzed with spearman rank correlation and ANOVA. Results revealed, small and medium-sized clusters were positive for cell proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) in control and slightly degenerated human discs, while large cell clusters were typically more abundant in severely degenerated and herniated discs. Large clusters associated with matrix fissures, proteoglycan loss, matrix metalloproteinase-1 (MMP-1), and Caspase-3. Spatial association findings were reconfirmed with SDS-PAGE that showed presence to these target markers based on its molecular weight. Controls, slightly degenerated discs showed smaller clusters, less proteoglycan loss, MMP-1, and Caspase-3. In conclusion, cell clusters in the early stages of degeneration could be indicative of repair, however sustained loading increases large cell clusters especially around microscopic fissures that accelerates inflammatory catabolism and alters cellular metabolism, thus attempted repair process initiated by cell clusters fails and is aborted at least in part via apoptosis.

키워드

과제정보

Research Grants from Indian Council of Medical Research (No. ICMR/5/7/1290-2015 RCH), Dr TMA Pai Grant (No. SMU/131/REG/TMAPURK/164/2020) for Polly Lama and Action Medical Research Grant (No. MS0549089/2016) for Trish Dolan and Michael A Adams.

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