Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis

Background Lumbar spinal stenosis (LSS) is a common cause of low back pain with degenerative spinal change in older adults. Telomeres are repetitive nucleoprotein DNA sequences of TTAGGG at the ends of chromosomes. Oxidative stress originates from an imbalance in pro-oxidant and antioxidant homeosta...

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Main Authors: Sinsuda Dechsupa, Wicharn Yingsakmongkol, Worawat Limthongkul, Weerasak Singhatanadgige, Sittisak Honsawek
Format: Article
Language:English
Published: PeerJ Inc. 2018-08-01
Series:PeerJ
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Online Access:https://peerj.com/articles/5381.pdf
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author Sinsuda Dechsupa
Wicharn Yingsakmongkol
Worawat Limthongkul
Weerasak Singhatanadgige
Sittisak Honsawek
author_facet Sinsuda Dechsupa
Wicharn Yingsakmongkol
Worawat Limthongkul
Weerasak Singhatanadgige
Sittisak Honsawek
author_sort Sinsuda Dechsupa
collection DOAJ
description Background Lumbar spinal stenosis (LSS) is a common cause of low back pain with degenerative spinal change in older adults. Telomeres are repetitive nucleoprotein DNA sequences of TTAGGG at the ends of chromosomes. Oxidative stress originates from an imbalance in pro-oxidant and antioxidant homeostasis that results in the production of reactive oxygen species (ROS). The purpose of this study was to investigate relative telomere length (RTL) and oxidative DNA damage in ligamentum flavum (LF) tissue from LSS patients. Methods Forty-eight patients with LSS participated in this study. Genomic DNA from non-hypertrophic and hypertrophic LF tissue were analyzed by real-time polymerase chain reaction for relative telomere length (RTL). 8-hydroxy 2′-deoxygaunosine (8-OHdG) levels were determined by using enzyme-linked immunosorbent assay. We cultivated LF fibroblast cells from patients in different ages (61, 66, and 77 years). After each cultivation cycle, we examined RTL and senescence-associated β-galactosidase (SA-β-gal) expression. Results The hypertrophic LF had significantly lower RTL than non-hypertrophic LF (P = 0.04). The levels of 8-OHdG were significantly higher in hypertrophic LF compared to non-hypertrophic LF (P = 0.02). With advancing cell culture passage, the number of cells in each passage was significantly lower in hypertrophic LF fibroblast cells than non-hypertrophic LF fibroblast cells. When evaluated with SA-β-gal staining, all senescent LF fibroblast cells were observed at earlier passages in hypertrophic LF compared with non-hypertrophic LF fibroblast cells. Discussion Our results showed that patients with LSS displayed an accelerated RTL shortening and high oxidative stress in hypertrophic LF. These findings implied that telomere shortening and oxidative stress may play roles in the pathogenesis of hypertrophic LF in lumbar spinal stenosis.
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spelling doaj.art-a26aaae19a9e48c2a8d9d66cba127b282023-12-03T10:15:31ZengPeerJ Inc.PeerJ2167-83592018-08-016e538110.7717/peerj.5381Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosisSinsuda Dechsupa0Wicharn Yingsakmongkol1Worawat Limthongkul2Weerasak Singhatanadgige3Sittisak Honsawek4Osteoarthritis and Musculoskeleton Research Unit, Department of Biochemistry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, ThailandDepartment of Orthopaedics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, ThailandDepartment of Orthopaedics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, ThailandDepartment of Orthopaedics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, ThailandOsteoarthritis and Musculoskeleton Research Unit, Department of Biochemistry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, ThailandBackground Lumbar spinal stenosis (LSS) is a common cause of low back pain with degenerative spinal change in older adults. Telomeres are repetitive nucleoprotein DNA sequences of TTAGGG at the ends of chromosomes. Oxidative stress originates from an imbalance in pro-oxidant and antioxidant homeostasis that results in the production of reactive oxygen species (ROS). The purpose of this study was to investigate relative telomere length (RTL) and oxidative DNA damage in ligamentum flavum (LF) tissue from LSS patients. Methods Forty-eight patients with LSS participated in this study. Genomic DNA from non-hypertrophic and hypertrophic LF tissue were analyzed by real-time polymerase chain reaction for relative telomere length (RTL). 8-hydroxy 2′-deoxygaunosine (8-OHdG) levels were determined by using enzyme-linked immunosorbent assay. We cultivated LF fibroblast cells from patients in different ages (61, 66, and 77 years). After each cultivation cycle, we examined RTL and senescence-associated β-galactosidase (SA-β-gal) expression. Results The hypertrophic LF had significantly lower RTL than non-hypertrophic LF (P = 0.04). The levels of 8-OHdG were significantly higher in hypertrophic LF compared to non-hypertrophic LF (P = 0.02). With advancing cell culture passage, the number of cells in each passage was significantly lower in hypertrophic LF fibroblast cells than non-hypertrophic LF fibroblast cells. When evaluated with SA-β-gal staining, all senescent LF fibroblast cells were observed at earlier passages in hypertrophic LF compared with non-hypertrophic LF fibroblast cells. Discussion Our results showed that patients with LSS displayed an accelerated RTL shortening and high oxidative stress in hypertrophic LF. These findings implied that telomere shortening and oxidative stress may play roles in the pathogenesis of hypertrophic LF in lumbar spinal stenosis.https://peerj.com/articles/5381.pdfRelative telomere length8-OHdGSA-beta-gal stainingLigamentum flavumLumbar spinal stenosis
spellingShingle Sinsuda Dechsupa
Wicharn Yingsakmongkol
Worawat Limthongkul
Weerasak Singhatanadgige
Sittisak Honsawek
Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis
PeerJ
Relative telomere length
8-OHdG
SA-beta-gal staining
Ligamentum flavum
Lumbar spinal stenosis
title Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis
title_full Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis
title_fullStr Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis
title_full_unstemmed Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis
title_short Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis
title_sort relative telomere length and oxidative dna damage in hypertrophic ligamentum flavum of lumbar spinal stenosis
topic Relative telomere length
8-OHdG
SA-beta-gal staining
Ligamentum flavum
Lumbar spinal stenosis
url https://peerj.com/articles/5381.pdf
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