| Abstract |
Back pain is the second leading cause of doctor visits and the leading cause of absenteeism in
developed countries. The etiology of low back pain involves all the anatomical components of
the lumbar spine, but the degeneration of intervertebral disc is responsible in 23% of cases with
sciatica. For this reason the study of the mechanisms of degeneration of the intervertebral disc
has gained much attention in the recent years. The human intervertebral disc is an avascular
structure with a large proportion of extracellular matrix which is regenerated by a small number
if cells. So, the integrity of these fewer cells is crucial and Akt / PKB tyrosine kinase act as an
important mediator in the cell survival process.
The degeneration of the intervertebral disc is a complex, multifactorial process with unknown
onset motive, where mechanic, biological and genetic factors, either alone or in synergy play the
most important role. The herniated intervertebral disc is the most important clinical
manifestation of this process of wear. The fact is that, over 90% of cases improve with
conservative treatment. This means that the body is able to activate various mechanisms at the
cellular level to correct the structural damage that has occurred.
These mechanisms are complex and intend (or comprise) the secretion of several inflammatory
mediators with various catabolic properties (interleukins, tumor necrosis factors and
metalloproteinases) and agents with anabolic properties (growth factors and tissue inhibitors of
metalloproteinases).
The aim of this study was to examine the simultaneous transcription levels of bone
morphogenetic proteins (BMP 1,2,7) and the full group of tissue inhibitors of metalloproteinases
(TIMPs 1,2,3,4) as well as of Akt / PKB in the same samples intervertebral disc hernia and the
potential association of the results with the clinical-pathological characteristics of patients with
symptoms of sciatica.
For this purpose mRNA levels were measured using quantitative PCR real time (real-time PCR)
on 63 samples of lumbar disc herniation from patients with sciatica symptoms and in 10
cadaveric samples as controls.
Our results are interesting because of the existence of multiple positive correlations. The analysis
of co-expression pairs showed a significant positive correlation between Akt1kai Akt3 in the
pathological group, suggesting a synergistic action between them, in the process of degeneration
of the intervertebral disc. In respect of the BMPs study, in the group of disc control the
transcriptional levels of BMP-1 are positively correlated with the levels of BMP-2. However, in
the group of pathologic discs, except for a co-expression observed between BMP-1 and BMP-2
mRNA, a significant negative correlation was observed between BMP-1 and BMP-7. Finally, in
the control group, TIMPs’s levels show no correlation, while the pathological group presents a
large number of pairwise correlations demonstrating that all four family members act in a
synergic way.
Smoking habits were found to have a positive correlation with pain intensity, suggesting an
unfavorable role for smoking in the regression process of herniated disc fragments. Our results
provide knowledge to the molecular profile of Akt / PKB tyrosine-kinase, tissue inhibitors of
metalloproteinases(TIMP1 to 4) and bone morphogenetic proteins(BMP1,2,7) in the herniated
intervertebral disc and highlights the relationship with the clinical and pathological
characteristics of the patients studied, strengthening the hypothesis of the involvement of these
agents in the natural history of the disease. The present study according to our opinion provides
another stone to our understanding of the complex mechanism that mediates the pathogenesis of
intervertebral disc herniation. However, further research is needed to elucidate the exact role of
the alleged players in this complicated process.
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Μελέτη της έκφρασης των οστικών μορφογενετικών πρωτεϊνών (BMPs) των αναστολέων των μεταλλοπρωτεϊνασών (TIMPs) και της Akt/PKB στην παθογένεια της κήλης του μεσοσπονδυλίου δίσκου
