Pathophysiology of the human intervertebral disc (original) (raw)
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A biological approach to treating disc degeneration: not for today, but maybe for tomorrow
Arthroplasty of the Spine, 2004
Intervertebral discs are characterized by their abundant extracellular matrix and low cell density, coupled with an absence of blood vessels, lymphatics, and nerves in all but the most peripheral annulus layers. In many respects, this absence leaves the disc prone to degeneration, because the cells have a large extracellular matrix to maintain without nociceptive feedback to limit and detect damage, and no source of repair through the vasculature.
Bioscience Horizons, 2009
Lower back pain (LBP) is a major cause of pain and disability. However, current treatment strategies are focused primarily on relieving its symptoms and have varying degrees of success. For future treatments to be proactive, they must target the underlying pathogenic alterations in cellular biology. Intervertebral disc degeneration (IVDD) has been linked to a high percentage of LBP cases, therefore, inhibition of the processes contributing to IVDD and, regeneration of the intervertebral disc (IVD) matrix lost during IVDD are the primary focuses of current research. Therapies aimed at the inhibition of the cytokine interleukin-1 that is increased during IVDD have been investigated as potential treatments aimed at inhibiting the pathogenic processes of IVDD. In addition, the application of growth factors, such as insulin-like growth factor, transforming growth factor and bone morphogenetic protein or alternatively replacement of abnormal IVD cells, either by injection of mesenchymal stem cells or autologous disc cell transplantation, has been investigated as potential therapeutic agents aimed at regeneration of the IVD matrix. However, for research into these therapeutic techniques to progress, a more detailed knowledge of the complex cellular biology of the IVD is required.
The Journal of Pathology, 2002
Until recently, material removed from the intervertebral disc (IVD) at surgery consisted either of 'loose bodies' from the centre of the IVD or discal tissue displaced (prolapsed) into the intervertebral root or spinal canals. This material is best regarded as a by-product of disc degeneration and therefore not representative of the disease process itself. Recent advances in surgical techniques, particularly anterior fusion, in which large segments of the anterior part of the IVD are excised with the anatomical relationships between different components intact, have generated material that can be investigated with modern molecular and cell biological techniques. This is an important area of study because degeneration of the lumbar IVDs is associated, perhaps causally, with low back pain, one of the most common and debilitating conditions in the West. 'Degeneration' carries implications of inevitable progression of wear-and-tear associated conditions. Modern research on human IVD tissue has shown that this is far from the case and that disruption of the micro-anatomy described as degeneration is an active process, regulated by locally produced molecules. The exciting consequence of this observation is the possibility of being able to inhibit or even reverse the processes of degeneration using targeted therapy.
The pathophysiology of disc degeneration: A CRITICAL REVIEW
Journal of Bone and Joint Surgery - British Volume, 2008
The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries.
Current reviews in musculoskeletal medicine, 2015
Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in disc diseases, including cytokines, chemokines, and proteases; advancements in disc disease diagnostics using imaging modalities; updates on studies examining the response of the intervertebral disc to injury; and recent developments in repair strategies, including cell-based repa...
The role of proteoglycans in aging, degeneration and repair of the intervertebral disc
Biochemical Society Transactions, 2002
The ability of the nucleus pulposus of the intervertebral disc to resist compressive loads is due to its high content of the proteoglycan aggrecan. Degeneration of the intervertebral disc is preceded and accompanied by a loss of aggrecan due to proteolysis. Biological repair of intervertebral disc degeneration should strive to restore aggrecan content to its optimal functional level. One approach to such repair is to supplement the degenerate nucleus with cells that are capable of aggrecan synthesis. Such cells can be supported in a biomolecular scaffold, but it is essential that the scaffold is compatible with high aggrecan retention if a functional tissue is to be attained.
The Spine Scholar, 2017
The unique properties of the intervertebral disc (IVD) are evident in its structural complexity and functional importance for spinal support and stability. The contributions of the different cellular and extracellular components to the function of the IVD depend on their distinctive molecular features and pathways. Disruption of these molecular pathways influences the pathological changes involved in IVD degeneration. Therefore, the molecular features of the IVD have been the focus of interest for many researchers seeking to elucidate its normal functioning, potential pathologies, and appropriate therapies. The aim of the present article is to review the molecular aspects of IVD development, specific cellular markers, and the interactions between cellular and extracellular components responsible for homeostasis, degeneration and potential therapies. The literature available via PubMed and Google Scholar was reviewed and the relevant references in review articles were searched manually. Spine Scholar 1:2-20, 2017
European Spine Journal, 2013
Background The intervertebral disc (IVD) is a complex cartilaginous structure which functions to resist biomechanical loads during spinal movement. It consists of the highly viscous cartilaginous nucleus pulposus, which is surrounded laterally by a thick outer ring of fibrous cartilage-the annulus fibrosus-and sandwiched inferiorly and superiorly by the cartilage end-plates. The main extracellular matrix molecules of the disc are collagens, proteoglycans, glycoproteins and elastin. The disc also contains appreciable amounts of water, matrix-degrading protease enzymes and their inhibitors, soluble signalling molecules and various metabolic breakdown products. Methods This review provides a comprehensive description of the biochemical composition of the extracellular matrix of the IVD and, specifically, the proteases involved in its molecular turnover. Quantitation of the turnover rates using racemization of aspartic acid as a molecular clock is also discussed. Conclusions Molecular turnover rates of the major constituent matrix macromolecules of the IVD are found to be particularly slow, especially in the case of collagen. Over a normal human life span, this slow turnover may compromise the structural integrity of the IVD extracellular matrix essential for normal physiological functioning.
Matrisome Profiling During Intervertebral Disc Development And Ageing
Scientific Reports
Intervertebral disc (IVD) degeneration is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. The changes that occur in the disc with age have been under investigation. However, a thorough study of ECM profiling is needed, to better understand IVD development and age-associated degeneration. As so, iTRAQ LC-MS/MS analysis of foetus, young and old bovine NPs, was performed to define the NP matrisome. The enrichment of Collagen XII and XIV in foetus, Fibronectin and Prolargin in elder NPs and Collagen XI in young ones was independently validated. This study provides the first matrisome database of healthy discs during development and ageing, which is key to determine the pathways and processes that maintain disc homeostasis. The factors identified may help to explain age-associated IVD degeneration or constitute putative effectors for disc regeneration. The intervertebral disc (IVD) is a complex structure capable of resisting spinal compression while allowing motion of intervertebral segments 1, 2. Besides water, it is mainly composed by extracellular matrix (ECM) molecules. These include collagens, proteoglycans (PGs) and other matrix proteins that contribute to the structural and mechanical function of the disc 3, 4. Matrix degrading enzymes are also present to regulate matrix breakdown, maintaining disc homeostasis 5. A young healthy disc consists of a highly plastic and hydrated region-the nucleus pulposus (NP)-and a network of collagen fibres oriented in sheets around the nucleus-the annulus fibrosus (AF), which provides tensile strength and confines the NP, limiting bulging 6. During disc degeneration and ageing, significant changes are observed in the IVD at both cell and tissue level. From birth, notochordal cells gradually disappear from the NP 7. Loss of cell density is accompanied by a shift towards a chondrocyte-like cell population 3 , less effective in NP-specific matrix synthesis 8. Ultimately this results in NP fibrous transformation, from a translucent gel to a more solid and cartilaginous tissue 1 making it difficult to distinguish between NP and AF 6. Alterations in the composition and mechanical properties of the surrounding environment will in turn influence NP cell function and behaviour, in terms of differentiation, metabolism, proliferation and survival 8. Along with cellular changes, NP matrix remodeling is also an early step in the ageing process. Apart from overall matrix breakdown caused by MMPs (matrix metalloproteinases) and ADAMTS (a desintegrin and metalloprotease with thrombospondin motifs) overexpression 7 , PG and collagen synthesis patterns 9, 10 , as well as fibre crosslinking 1 are also altered. This inhibits matrix turnover and, together with the already limited repair response, leads to dehydration and progressive ECM disorganization. Furthermore, it promotes mechanical failure, annular tears and many of the characteristic features of disc degeneration 6. Over time, type II collagen is replaced by
A Brief Review of the Degenerative Intervertebral Disc Disease
Medical Archives, 2019
Introduction: The degenerative processes of the intervertebral disc represent an important cause of morbidity in everyday clinical practice, exerting burden on patients and clinicians treating them. Numerous factors may initiate degenerative processes, which most commonly affect the nucleus pulposus and ultimately influence the biomechanics of the whole spine. Aim: This paper provides an overview from the literature about the process, causes and mechanisms of disc degeneration and the associated factors. Methods: The scientific literature was reviewed through PubMed, Medline and Science Direct. The articles were chosen in correlation with the study objective and their scientific relevance. Results: Many mechanical factors, such as mechanical, traumatic, genetic and nutritional, may affect the integrity of the intervertebral disc. The degenerative processes involve the structural damage of the intervertebral disc and the changes in number and composition of cells. The main factor in the degeneration of the intervertebral disc is the loss of proteoglycans. Degenerative changes of the disc are connected to damage of adjacent structures, leading to functional changes, higher susceptibility to injuries and clinical signs and symptoms. Conclusions: Degenerative disease of the intervertebral disc remains a significant health problem. Besides standard conservative and surgical treatment, techniques of regenerative therapy are becoming very promising, although still in the experimental phase.