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Apoptosis of human ...
Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor-mediated and mitochondrial-dependent pathways.
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Tschoeke, Sven K (author)
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Hellmuth, Markus (author)
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Hostmann, Arwed (author)
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- Robinson, Yohan, 1977 (author)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för ortopedi,Institute of Clinical Sciences, Department of Orthopaedics,Ortopedi
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Ertel, Wolfgang (author)
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Oberholzer, Andreas (author)
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Heyde, Christoph-E (author)
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(creator_code:org_t)
- 2008-02-26
- 2008
- English.
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In: Journal of orthopaedic research : official publication of the Orthopaedic Research Society. - : Wiley. - 1554-527X .- 0736-0266. ; 26:7, s. 999-1006
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Abstract
Subject headings
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- Post-traumatic disc degeneration with consecutive loss of reduction and kyphosis remains a debatable issue within both the operative and nonoperative treatment regimen of thoracolumbar spine fractures. Intervertebral disc (IVD) cell apoptosis has been suggested to play a vital role in promoting the degeneration process. To evaluate and compare apoptosis-regulating signaling mechanisms, IVDs were obtained from patients with thoracolumbar spine fractures (n = 21), patients suffering from symptomatic IVD degeneration (n = 6), and from patients undergoing surgical resection of a primary vertebral tumor (n = 3 used as control samples). All tissues were prospectively analyzed in regards to caspase-3/7, -8, and -9 activity, apoptosis-receptor expression levels, and gene expression of the mitochondria-bound apoptosis-regulating proteins Bax and Bcl-2. Morphologic changes characteristic for apoptotic cell death were confirmed by H&E staining. Statistical significance was designated at p < 0.05 using the Student's t-test. Both traumatic and degenerative IVD demonstrated a significant increase of caspase-3/7 activity with evident apoptosis. Although caspase-3/7 activation was significantly greater in degenerated discs, both showed equally significant activation of the initiator caspases 8 and 9. Traumatic IVD alone demonstrated a significant increase of the Fas receptor (FasR), whereas the TNF receptor I (TNFR I) was equally up-regulated in both morbid IVD groups. Only traumatic IVD showed distinct changes in up-regulated TNF expression, in addition to significantly down-regulated antiapoptotic Bcl-2 protein. Our results suggest that post-traumatic disc changes may be promoted and amplified by both the intrinsic mitochondria-mediated and extrinsic receptor-mediated apoptosis signaling pathways, which could be, in part, one possible explanation for developing subsequent disc degeneration.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Ortopedi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Orthopaedics (hsv//eng)
Keyword
- Adult
- Aged
- Apoptosis
- physiology
- Caspases
- metabolism
- Down-Regulation
- Female
- Humans
- Intervertebral Disc
- enzymology
- metabolism
- physiopathology
- Lumbar Vertebrae
- injuries
- Male
- Middle Aged
- Mitochondria
- metabolism
- Prospective Studies
- Proto-Oncogene Proteins c-bcl-2
- metabolism
- Signal Transduction
- physiology
- Spinal Diseases
- metabolism
- Spinal Fractures
- metabolism
- Thoracic Vertebrae
- injuries
- fas Receptor
- metabolism
- Orthopaedics
Publication and Content Type
- ref (subject category)
- art (subject category)
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