EU Project Web Page

Eurodisc

Intervertebral Disc Degeneration:

Interplay of Age,
Environmental and Genetic Factors

Institute of Biology, N.C.S.R. Demokritos, Athens, Greece; Technion - Israel Institute of Technology, Haifa, Israel; Oxford University, Oxford, UK; RJAH Orthopaedic Hospital, Oswestry, UK;
Technische Universiteit Eindhoven, Eindhoven, The Netherlands; University of Helsinki, Helsinki, Finland; University of Ulm, Ulm, Germany

Home

Objectives

Achievements

Progress

Publications

Consortium

OBJECTIVES AND EXPECTED ACHIEVEMENTS

Overview

The function of the intervertebral disc depends on the composition and organisation of it's extracellular matrix. Degeneration, which is clearly age-related, arises when damaged matrix constituents cannot be adequately repaired. Consequent changes in matrix composition and organisation affect the mechanical functioning of the disc and nutritional pathways within the tissue. Such matrix changes may alter cellular metabolism adversely and also permit the ingrowth of blood vessels and nerves into the previously avascular, aneural disc. The objectives of the project are thus to examine the interplay of ageing, genotype and environmental factors in disc matrix degeneration. This project will provide (1) a multidisciplinary approach to the aetiopathology of disc degeneration, (2) an objective diagnostic scheme for clinical use and (3) new diagnostic tools. It will also aid in the development of new treatments for disc degeneration and spinal stenosis.

Hypotheses
- A cascade of events forms a degenerative pathway that leads to disc degeneration
- That extracellular matrix breakdown -
  1. arises in part because changes in the cells' environment stimulate catabolic cellular pathways;
  2. affects both nutritional pathways and the mechanical micro-environment of the cell;
  3. allows ingrowth of blood vessels and nerves; and
  4. prevents micro-repair thus promoting further matrix breakdown
- These events perpetuate the degenerative pathway

Overall Aims
- To delineate the pathways of disc degeneration
- To use this information to provide objective diagnostic means for the purposes of targeted treatments and prevention of intervertebral disc disorders

Objectives
- Study turnover
- Determine whether the altered matrix allows ingrowth of blood vessels and nerves and isolate matrix components responsible for this
- Determine how the altered matrix affects aspects of mechanical function and the mechanical environment of the cells
- Determine how mechanical and nutrient stresses affect disc cell metabolism and their capacity to promote tissue repair
- Investigate signalling pathways involved
- Determine the role of age and genotype in mediating all these cell-induced changes
- Examine a population-based twin data base for age-gene-environmental associations with disc degeneration and relate these results to those obtained at a cellular level
- Use this information to provide objective diagnostic criteria via a diagnostic scheme, specific MRI degeneration parameters and intradiscal microelectrode measurements

Expected Achievements
The overall benefits to the health sector will be threefold:
1. The objective diagnostic grading scheme will increase effectiveness and targetting of treatment
2. Preventative measures can be more specific and better targeted by taking individual variability into account
3. Better understanding of the aetiopathogenesis of disc degeneration will enable development of novel therapies and rational preventative therapies
The project will also lead to direct applications:
1. Development of diagnostic measures of nutrient supply to human disc in vivo
2. Optimisation of a disc prosthesis
3. Novel diagnostic MRI sequences

Intervertebral Disc Degeneration:

Interplay of Age, Environmental and Genetic Factors

Interplay of Age,
Environmental and Genetic Factors