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HUMAN INTERVERTEBRAL DISC AGGRECAN INHIBITS ENDOTHELIAL CELL MIGRATION IN VITRO.



Abstract

Background: Increased nerve growth into degenerated intervertebral discs is associated with discogenic low back pain [1]. Many of these growing nerves are in neo-vascularised areas of the tissue [1,2] and endothelial cells that penetrate the disc express neurotrophic factors [3]. Thus, disc neovascularisation and disc innervation may be closely linked. Whilst disc aggrecan has been found to inhibit sensory nerve growth in vitro [4], the effects of disc aggrecan on endothelial cells are unknown.

Methods/Results: Adapting in vitro assays used previously [4], with HMEC-1 and EAhy-926 cell lines as models of endothelial cell growth, we found that disc aggrecan inhibited endothelial cell migration in a dose-dependent manner. Endothelial cells traversed over collagen substrates until they encountered disc aggrecan substrates (1mg/ml human aggrecan), where they either stopped migrating or, more commonly, changed their direction of movement and aligned to the collagen:aggrecan border (Figure 1). After reaching the aggrecan border, some endothelial cells also migrated away from the disc aggrecan. At lower concentrations of disc aggrecan (0.01mg/ml), no such inhibition of endothelial cell growth was seen.

Conclusions: Loss of aggrecan, increased innervation and neovascularisation are all marked features of disc degeneration [1,2,5]. This study provides evidence that disc aggrecan inhibits endothelial migration and therefore supports a hypothesis that a loss of aggrecan from degenerated discs predisposes the tissue to vascular invasion.

The abstracts were prepared by Editorial Secretary, Dr Charles Pither. Correspondence should be addressed to SBPR at the Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London WC2A 3PN

References:

[1] Freemont et al (1997) Lancet350: 178–81. Google Scholar

[2] Johnson WEB et al (2001) Spine26: 2550–7. Google Scholar

[3] Freemont ei al (2002) J Path197: 286–92. Google Scholar

[4] Johnson WEB et al (2002) Arth Rheum46: 2658–64. Google Scholar

[5] Lyons et al (1981) BBA673: 443–53. Google Scholar