Why do intervertebral discs degenerate ? Presentation of the European research project EURODISC.

Back pain is a very common burden that almost everybody experiences at least once in his lifetime. It leads to considerable loss of productivity in the working population, which together with direct health and benefit costs, make it one of the expensive health problems in the western world. The causes of back pain are poorly understood but in most cases correlate strongly with problems caused by disc degeneration. Relatively little basic research has been carried out into the causes of disc degeneration and fundamental questions remain unanswered. Why do intervertebral discs degenerate? Is this problem genetically determined? What is the impact of age, nutrition and physical loading on degeneration? The purpose of EURODISC was to investigate these questions through a multidisciplinary researchconsortium (Figure 1). Figure 1: The Eurodisc consortium, a multidisciplinary research network focussing on the intervertebral disc. The locations of the 7 project partner groups from 6 European countries is shown. EURODISC consists of 7 research groups from 6 European countries viz. UK (Oxford and Oswestry), Holland (Eindhoven), Finland (Helsinki), Greece (Athens), Israel (Haifa) and Germany (Ulm), funded by the European Union in 2003 for a duration of three years. Each group has expert knowledge and experience in different disciplines, including engineering, cell biology, genetics, radiology, biochemistry and spinal surgery. Close collaborations between the project partners has created a multidisciplinary network focussing on the intervertebral disc. Tissue samples from patients undergoing disc surgery are collected and exchanged between the partners from all EURODISC research groups and studied via histology, biochemistry and cell biology. In parallel, DNA from blood samples of all donors and matched ‘controls’ is assayed for genetic variations possibly associated with disc degeneration. Questionnaires with information regarding the back pain history of all individuals are collected and studied. The data gathered from all aspects of the study is entered into a common database for statistical analysis of correlations between tissue and cell behaviour and genetic polymorphisms. The multidisciplinary nature of the consortium enables different aspects of degenerative change to be studied on specimens from the same patient. Results of histological and biochemical investigations provide evidence for changes in tissue structure, cellular parameters and composition of matrix macromolecules during degeneration. One if the most noticeable changes is the degradation and loss of proteoglycan, a major macromolecule of disc matrix responsible for its hydration and load-bearing properties. The fall in proteoglycan concentration appears to permit the greater degree of vascularisation and innervation observed in degenerated discs. Cellular changes have been observed, such as an increased degree of senescence in herniated discs. Other factors also influence cellular behaviour; mechanical loading affects synthesis and degradation of the intervertebral disc matrix via enhancement or inhibition of gene expression for the respective proteins involved in these processes. Mechanical forces also stimulate disc cells to release signalling molecules that influence proliferative activity of disc cells. In parallel to the analysis of disc tissue, cells, and blood samples, a finite element model that includes proteoglycan-dependent osmotic swelling and collagen fiber orientation properties has been developed. This mathematical model can be used for predicting changes of cellular environment of EURODISC samples. Genetic factors have a very strong influence on disc degeneration as demonstrated by twin studies. DNA-genotyping of blood samples from EURODISC patients and controls will allow the identification of variations (single nucleotide polymorphisms) in genes associated with different aspects of disc degeneration. It is hoped that these investigations may contribute to a better understanding of the factors influencing intervertebral disc degeneration. This should give rise to the development of preventional concepts, more objective diagnostic schemes and improved, targeted treatments for intervertebral disc diseases and hence, hopefully, of back pain.