Occurrence and regional distribution of apoptosis in scoliotic discs.
METHODS
Seventy surgically obtained intervertebral discs from 9 patients with idiopathic and 7 patients with neuromuscular scoliosis were analyzed for the regional distribution of apoptosis.


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


BACKGROUND
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.


CONCLUSIONS
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.
Chen
Bohua
B
Division of Experimental Orthopedics, Orthopedic University Hospital, Heidelberg, Germany.
Fellenberg
Jörg
J
Wang
Haili
H
Carstens
Claus
C
Richter
Wiltrud
W
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D002648:Child; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000737:chemistry* / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D012600:Scoliosis / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D048069:Tumor Necrosis Factors / Q000096:biosynthesis / Q000235:genetics
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors