Advertisement for orthosearch.org.uk
Orthopaedic Proceedings Logo

Receive monthly Table of Contents alerts from Orthopaedic Proceedings

Comprehensive article alerts can be set up and managed through your account settings

View my account settings

Visit Orthopaedic Proceedings at:

Loading...

Loading...

Full Access

RESPONSE OF HUMAN INTERVERTEBRAL DISC CELLS TO IL-1



Abstract

Objective and Background: This study investigated the effects of IL-1 on human intervertebral disc cells (IVD). IL-1 has been implicated in the degradation of IVD, in particular the up-regulation of Matrix Metalloproteinases (MMPs) and the down regulation of proteoglycan synthesis. However very little is known of the effects of IL-1 on human IVD cells. Here, we have investigated the effects of both IL-1 α and IL-1 β on nucleus pulposus (NP) and Annulus fibrosus (AF) cells isolated from human degenerate IVD.

Methods: Human IVD tissue was obtained from disc replacement surgery and separated into NP and AF tissue, cells were cultured within an alginate bead system for 5 weeks before treatment with IL-1 α and IL-1 β for 48 hours. Following treatment, RNA was extracted and Real time RT-PCR was performed to investigate gene expression of IL-1 gene family, matrix proteins and degrading enzymes MMPs and ADAMTS.

Results: Interleukin 1 α showed a more potent response than IL-1 β and in addition NP cells were more sensitive than AF cells. In summary, IL-1 showed a positive feedback loop causing an up-regulation of α and β genes. IL-1 Ra was also up-regulated but to a lesser extent than IL-1 α and IL-1 β. A negative feedback loop was seen with inhibition of the IL-1 receptor gene upon treatment with IL-1. MMPs and ADAMTS showed up-regulation upon treatment with IL-1. In addition IL-1 down regulated the matrix protein’s collagen type II and Aggrecan.

Conclusions: This study demonstrates that IL-1 causes up-regulation in discal cells of the major degrading enzymes involved in discal degeneration, and a down regulation of the major matrix components within the IVD. Suggesting that IL-1 plays a major in process of discal degeneration.

Correspondence should be addressed to the editorial secretary: Dr Charles Pither, c/o British Orthopaedic Society, Royal College of Surgeons, 35-43 Lincoln’s Inn Fields, London WC2A 3PN.