RESEARCH - Regulation of catabolic gene expression in normal and degenerate human intervertebral disc cells: implication for the pathogenesis of intervertebral disc degeneration

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Arthritis Research & Therapy 2009, 11:R65doi:10.1186/ar2693

Published: 12 May 2009

Research article

Regulation of catabolic gene expression in normal and degenerate human

intervertebral disc cells: implications for the pathogenesis of

intervertebral disc degeneration

S Jane Millward-Sadler , W Costello , J Freemont and

Judith A Hoyland

Abstract (provisional)

Introduction

The aim of this study was to compare the effects of tumour necrosis

factor (TNF)-a and interleukin (IL)-1b on protease and catabolic

cytokine and receptor gene expression in normal and degenerate human

nucleus pulposus cells in alginate culture.

Methods

Cells isolated from normal and degenerate nucleus pulposus regions of

human intervertebral discs were cultured in alginate pellets and

stimulated by the addition of 10 ng/ml TNFa or IL1b for 48 hours prior

to RNA extraction. Quantitative real-time polymerase chain reaction

(PCR) was used to assess the effect of TNFa or ILb stimulation on the

expression of matrix metalloproteinases (MMP) 3, 9 and 13, TNFa,

TNF-receptor1 (TNF-R1), TNF-receptor2 (TNF-R2), IL1a, IL1b, IL1

receptor1 (IL1R1) and IL1 receptor antagonist (IL1Ra).

Results

MMP3 and MMP9 gene expression was upregulated to a greater level by

IL1b than TNFa. MMP13 was upregulated by both cytokines to a similar

extent. TNFa and TNF-R2 expression were upregulated by both TNFa and

ILb, while TNF-R1 expression was not significantly affected by either

cytokine. IL1b and IL1Ra expression were significantly upregulated by

TNFa, while IL1a and IL1R1 were unchanged.

Conclusions

TNFa does not induce MMP expression to the same degree as stimulation

by IL1b, but it does act to upregulate IL1b expression as well as TNFa

and TNF-R2. The net result of this would be an increased inflammatory

environment and accelerated degradation of the matrix. These results

support the hypothesis that while TNFa may be an important initiating

factor in matrix degeneration, IL1b plays a greater role in

established pathological degradation.

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http://arthritis-research.com/content/pdf/ar2693.pdf

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