In-situ-Analyse von Pathomechanismen der humanen Bandscheibendegeneration

Abstract

Low back pain is one of the major causes of pain and disability in the western world, with a constantly rising life-time prevalence of approximately 60-85 %. Degeneration of the intervertebral disc is believed to be a major cause of low back pain. Semiquantitative macroscopic and microscopic changes of the intervertebral disc were assessed and classified. Furthermore additional methods, such as immunohistochemistry, in situ hybridization and in situ zymography were used to analyze phenotypic cellular and matrix changes. We have developed and tested a practicable, valid and reliable histological classification system for lumbar discs which can serve as a morphological reference framework to allow more sophisticated molecular biological studies on the pathogenesis of ageing and degeneration of discs. Secondly, we were able to demonstrate that intrinsic (genetic) and extrinsic (e.g. overweight) factors have a profound effect on the process of disc degeneration. Cells with a notochord-like phenotype are present in a considerable fraction of adult lumbar intervertebral discs. The presence of these cells is associated with distinct features of (early) age-related disc degeneration. During the process of disc degeneration, the intervertebral disc shows a progressive and significant reduction in height due to tissue resorption. This matrix loss is related to an imbalance between matrix synthesis and degradation. During this process an inflammatory reaction takes place and resident disc cells are causatively involved. In summary, disc degeneration is a multifactorial disease with a strong intrinsic (hereditary) and extrinsic (e.g. mechanical factors) background. The process starts as early as in the second decade of life and shows high interindividual differences. The loss of regenerative capacity in the intervertebral disc is probably related to the loss of stem cells, e.g. notochord-like cells. Resident disc cells are involved in the inflammatory reaction with increased matrix degradation, resorption and reduced matrix synthesis.