Current understanding of cellular and molecular events in intervertebral disc degeneration: implications for therapy (original) (raw)
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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.
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...
SAGE open medicine, 2018
Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving st...
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, 2012
Purpose Disc degeneration, and associated low back pain, are a primary cause of disability. Disc degeneration is characterized by dysfunctional cells and loss of proteoglycans: since intervertebral tissue has a limited capacity to regenerate, this process is at present considered irreversible. Recently, cell therapy has been suggested to provide more successful treatment of IVD degeneration. To understand the potential of cells to restore IVD structure/function, tissue samples from degenerated IVD versus healthy discs have been compared. Methods Discal tissue from 27 patients (40.17 ± 11 years) undergoing surgery for degenerative disc disease (DDD), DDD ? herniation and congenital scoliosis, as controls, was investigated. Cells and matrix in the nucleus pulposus (NP) and annulus fibrosus (AF) were characterized by histology. AF-and NP-derived cells were isolated, expanded and characterized for senescence and gene expression. Three-dimensional NP pellets were cultured and stained for glycosaminoglycan formation. Results Phenotypical markers of degeneration, such as cell clusters, chondrons, and collagen disorganization were seen in the degenerate samples. In severe degeneration, granulation tissue and peripheral vascularization were observed. No correlation was found between the Pfirrmann clinical score and the extent of degeneration. Conclusion The tissue disorganization in degenerate discs and the paucity of cells out of cluster/chondron association, make the IVD-derived cells an unreliable option for disc regeneration.
Pathophysiology of the human intervertebral disc
Intervertebral disc degeneration is a common invalidating disorder that can affect the musculoskeletal apparatus in both younger and older ages. The chief component of the intervertebral disc is the highly organized extracellular matrix; maintenance of its organization is essential for correct spinal mechanics. The matrix components, mainly proteoglycans and collagens, undergo a slow and continuous cell-mediated turnover process that enables disc cells to adapt their environment to external stimuli. Cellular senescence and a history of chronic abnormal loading can upset this balance, leading to progressive tissue failure that results in disc degeneration. Although biological treatment approaches to disc repair are still far to come, advances in our understanding of disc biochemistry and in defining the role of genetic inheritance have provided a starting point for developing new concepts in the diagnosis, therapy and prevention of disc degeneration.
Histology and histopathology, 2007
Degeneration of the intervertebral disc (IVD) is a major cause of low back pain affecting a large percentage of the population at some point in their lives. Consequently IVD degeneration and its associated low back pain has a huge socio-economic impact and places a burden on health services world-wide. Current treatments remove the symptoms without treating the underlying problem and can result in reoccurrence in the same or adjacent discs. Tissue engineering offers hope that new therapies can be developed which can regenerate the IVD. Combined with this, development of novel biomaterials and an increased understanding of mesenchymal stem cell and IVD cell biology mean that tissue engineering of the IVD may soon become a reality. However for any regenerative medicine approach to be successful there must first be an understanding of the biology of the tissue and the pathophysiology of the disease process. This review covers these key areas and gives an overview of the recent developm...
Studies of Molecular Changes in Intervertebral Disc Degeneration in Animal Model
Acta Ortopédica Brasileira, 2016
Objective: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model. Methods: Wistar rats underwent intervertebral disc degeneration through 20-gauge needle puncture, and 360° rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15 th and 28 th days after degenerative induction. Results: Fifteen days after the induction of intervertebral disc degeneration, significant changes were observed, such as reduction in the expression metalloprotease-9 (MMP9) and interleukins (IL-6 and IL-10). There was a significant increase in the expression of vascular endothelial growth factor (VEGF) and caspase-3. However, different alterations in the ECM were observed at 28 days, the level of collagen I, metalloprotease-2 (MMP2) and caspase-3 were enhanced. Furthermore, expression of heparanase isoforms (HPSE1 and HPSE2) mRNA were increased in the degenerative intervertebral disc. Conclusion: The different profiles of ECM molecules observed during the intervertebral disc degeneration suggest that molecular processes such as ECM remodeling, neovascularization, apoptosis and inflammation occur. Experimental Study.
The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain
Rheumatology, 2008
In 2007, three times as many peer reviewed publications covering the biology and biotherapeutics of intervertebral disc (IVD) disease appeared in the literature than in 1997. This is testimony to the upsurge in interest in the IVD, mainly driven by the openings that modern molecular pathology has generated to investigate mechanisms of human disease and the potential offered by novel therapeutic technologies to use data coming from these studies to positively influence chronic discogenic back pain and sciatica. Molecular pathology has shown IVD degeneration, a major cause of low back pain, to be a complex, active disorder in which disturbed cytokine biology, cellular dysfunction and altered load responses play key roles. This has translated into a search for target molecules and disease processes that might be the focus of future, evidence-based therapies for back pain. It is not possible to describe the totality of advances that have been made in understanding the biology of the IVD in recent years, but in this review those areas of biology that are currently influencing, or could conceivably soon impinge on, clinical thinking or practice around IVD degeneration and discogenic back pain are described and discussed.
Degeneration of the intervertebral disc with new approaches for treating low back pain
Journal of neurosurgical sciences, 2015
This review paper discusses the process of disc degeneration and the current understanding of cellular degradation in patients who present with low back pain. The role of surgical treatment for low back pain is analysed with emphasis on the proven value of spinal fusion. The interesting and novel developments of stem cell research in the treatment of low back pain are presented with special emphasis on the importance of the cartilaginous end plate and the role of IL-1 in future treatment modalities.