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Occurrence and Regional Distribution of Apoptosis in Scoliotic Discs

Chen, Bohua MD; Fellenberg, Jörg PhD; Wang, Haili MD; Carstens, Claus MD; Richter, Wiltrud PhD

doi: 10.1097/01.brs.0000154652.96975.1f
Basic Science

Study Design. Seventy surgically obtained intervertebral discs from 9 patients with idiopathic and 7 patients with neuromuscular scoliosis were analyzed for the regional distribution of apoptosis.

Objectives. To investigate the role of apoptotic mechanisms in scoliotic discs.

Summary of Background Data. The reasons for the development of scoliosis are complex and yet not completely understood. In herniated lumbar disc tissue, increased apoptosis and a high expression of Fas and Fas ligand and caspase-3 activity have already been reported, suggesting a pivotal role of apoptotic mechanisms in intervertebral disc degeneration. In scoliotic discs, cell death was correlated with disc deformity and changes in nutrient supply and metabolic levels. The role of apoptosis in scoliotic discs, however, is still unclear.

Methods. Apoptosis was determined by terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and poly(ADP-ribose) polymerase (PARP) p85 immunohistochemistry. Expression of Fas and Fas-ligand was analyzed by immunohistochemistry and reverse transcription polymerase chain reaction analysis.

Results. In all samples analyzed, apoptotic cells could be detected in the nucleus, anulus, and endplate. The number of apoptotic cells was significantly higher in the nucleus compared to the other areas and in the apex versus the nonapex discs. There was no difference between the discs of idiopathic and neuromuscular scoliosis and between the 2 age groups studied (10–17 years and 17–48 years, respectively). A strong expression of Fas and Fas-ligand could be detected in all samples.

Conclusion. Increased numbers of apoptotic cells in the nucleus of scoliotic discs and the apex disc suppose a pivotal role of programmed cell death for the progression of this common disorder. The simultaneous increase of Fas and Fas-ligand expression in areas with increased cell death point to an activation of the apoptotic process via the Fas/Fas-L system.

The role of apoptotic mechanisms in scoliotic discs was investigated in 70 surgically obtained intervertebral discs by immunohistochemistry and reverse transcription polymerase chain reaction. A significantly elevated number of apoptotic cells could be detected in the nucleus compared to the other areas and in the apex versus the nonapex discs.

From the Division of Experimental Orthopedics, Orthopedic University Hospital, Heidelberg, Germany.

Supported by a grant from the Orthopedic University Hospital, Heidelberg, Germany.

Acknowledgment date: January 14, 2004. First revision date: March 5, 2004. Acceptance date: March 11, 2004.

Dr. Chen and Dr. Fellenberg share first authorship.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Foundation funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Dr. Jörg Fellenberg, PhD, Division of Experimental Orthopedics, Orthopedic University Hospital, Heidelberg, Schlierbacher Landstrate 200a, Heidelberg 69118, Germany; E-mail: joerg.fellenberg@ok.uni-heidelberg.de

© 2005 Lippincott Williams & Wilkins, Inc.