title: Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor-mediated and mitochondrial-dependent pathways.
abstract: 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.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Charité-University Hospitals Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany.
authors.forename: Sven K
authors.initials: SK
authors.lastname: Tschoeke
authors.forename: Markus
authors.initials: M
authors.lastname: Hellmuth
authors.forename: Arwed
authors.initials: A
authors.lastname: Hostmann
authors.forename: Yohan
authors.initials: Y
authors.lastname: Robinson
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ertel
authors.forename: Andreas
authors.initials: A
authors.lastname: Oberholzer
authors.forename: Christoph-E
authors.initials: CE
authors.lastname: Heyde
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000293:injuries*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013122:Spinal Diseases / Q000378:metabolism*; D016103:Spinal Fractures / Q000378:metabolism*; D013904:Thoracic Vertebrae / Q000293:injuries*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D020169:Caspases