Abstract

Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, interleukin-1β, interleukin-1 receptor) combined with low expression of anti-catabolic factor (metalloproteinase inhibitor 3) (P<0.0001). This study might contribute to inhibit inflammatory catabolism of cervical discs.

Highlights

  • After middle age many people experience pain symptoms of cervical disc degeneration

  • Previous publications have analysed the pathology of cervical disc degeneration only from a morphologic view point using magnetic resonance imaging (MRI), which does not address the issue of biological treatment approaches

  • Degenerative Cervical nucleus pulposus (NP) Cell Proliferation Rates 46105 degenerative cervical NP cells were cultured in collagen I

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Summary

Introduction

After middle age many people experience pain symptoms of cervical disc degeneration. Our current work is the first investigation concerning the endogenous expression patterns of ECM-associated proteins in degenerative cervical disc cells. The anatomical and mechanical differences might lead to functional modifications in cervical disc cells. These reasons suggest that biomolecular results from lumbar disc cells should not be directly projected onto cervical disc cells without any similar investigations. Previous publications have not yet displayed the biomolecular differences or similarities between lumbar and cervical disc. The data of the current study address for the first time the biomolecular issue of cervical disc degeneration and might contribute valuably to gene therapeutic approaches of painful intervertebral disc degeneration

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