Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor‐mediated and mitochondrial‐dependent pathways |
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| Authors: | Sven K. Tschoeke Markus Hellmuth Arwed Hostmann Yohan Robinson Wolfgang Ertel Andreas Oberholzer Christoph‐E. Heyde |
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| Affiliation: | 1. Department of Trauma and Reconstructive Surgery, Charité–University Hospitals Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany;2. Department of Orthopaedic Surgery, Klinik Pyramide am See, Zurich, Switzerland |
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| 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. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:999–1006, 2008 |
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| Keywords: | intervertebral disc apoptosis trauma caspase degeneration |
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