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Karin Wuertz

Bio: Karin Wuertz is an academic researcher from University of Zurich. The author has contributed to research in topics: Intervertebral disc & Proinflammatory cytokine. The author has an hindex of 23, co-authored 29 publications receiving 1921 citations. Previous affiliations of Karin Wuertz include ETH Zurich & University of Vermont.

Papers
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Journal ArticleDOI
TL;DR: The current state of knowledge concerning the inflammatory and catabolic molecular pathways of intervertebral disc disease (IDD) are summarized, with a detailed description of NF-kB and MAP kinase-mediated signal transduction in disc cells, and the emerging novel molecular treatment modalities for IDD are discussed.
Abstract: Painful intervertebral disc disease is characterised not only by an imbalance between anabolic (i.e., matrix synthesis) and catabolic (i.e., matrix degradation) processes, but also by inflammatory mechanisms. The increased expression and synthesis of matrix metalloproteinases and inflammatory factors is mediated by specific signal transduction, in particular the nuclear factor-kappaB (NF-kB) and mitogen-activated protein kinase (MAPK)-mediated pathways. NF-kB and MAPK have been identified as the master regulators of inflammation and catabolism in several musculoskeletal disorders (e.g., osteoarthritis), and recently growing evidence supports the importance of these signalling pathways in painful disc disease. With continuing research exploiting in vitro and in vivo model systems to elucidate the roles of these pathways in disc degeneration, it may be possible in the near future to specifically target these major inflammatory / catabolic signalling pathways to treat painful degenerative disc disease. In this perspective, we aim to summarise the current state of knowledge concerning the inflammatory and catabolic molecular pathways of intervertebral disc disease (IDD), with a detailed description of NF-kB and MAP kinase-mediated signal transduction in disc cells. Furthermore, we will discuss the emerging novel molecular treatment modalities for IDD using pharmacological inhibitors targeting these pathways.

201 citations

Journal ArticleDOI
TL;DR: Data on the gene and protein level is provided, which highlights the key role of MMP-3 in the degenerative cascade leading to symptomatic disc degeneration and herniation and Control of the proteolytic activity of M MP-3 may, therefore, come into the focus when aiming to develop new treatment options for earlyDisc degeneration.
Abstract: The disruption of the extracellular disc matrix is a major hallmark of disc degeneration. This has previously been shown to be associated with an up-regulation of major matrix metalloproteinase (MMP) expression and activity. However, until now hardly any data are available for MMP/TIMP regulation and thereby no concept exists as to which MMP/TIMP plays a major role in disc degeneration. The objective of this study was, therefore, to identify and quantify the putative up-regulation of MMPs/TIMPs on the mRNA and protein level and their activity in disc material in relation to clinical data and histological evidence for disc degeneration. A quantitative molecular analysis of the mRNA expression levels for the MMPs (MMPs-1, -2, -3, -7, -8, -9, -13) and the MMP inhibitors (TIMPs-1 and -2) was performed on 37 disc specimens obtained from symptomatic disc herniation or degeneration. In addition, disc specimens from patients without disc degeneration/herniation (=controls) were analyzed. Expression of MMPs-1, -2, -3, -7, -8, -9, -13 and TIMPs-1, -2 was analyzed using quantitative RT-PCR, normalized to the expression level of a house keeping gene (GAPDH). Gene expression patterns were correlated with MMP activity (in situ zymography), protein expression patterns (immunohistochemistry), degeneration score (routine histology) and clinical data. MMP-3 mRNA levels were consistently and substantially up-regulated in samples with histological evidence for disc degeneration. A similar but less pronounced up-regulation was observed for MMP-8. This up-regulation was paralleled by the expression of TIMP-1 and to a lesser extent TIMP-2. In general, these findings could be confirmed with regard to protein expression and enzyme activity. This study provides data on the gene and protein level, which highlights the key role of MMP-3 in the degenerative cascade leading to symptomatic disc degeneration and herniation. Control of the proteolytic activity of MMP-3 may, therefore, come into the focus when aiming to develop new treatment options for early disc degeneration.

169 citations

Journal ArticleDOI
TL;DR: This review provides information on the most relevant inflammatory mediators during different types of disk diseases and explains how these factors can induce disk degeneration and the development of discogenic and sciatic/radiculopathic pain.
Abstract: Although degeneration of the intervertebral disk has historically been described as a misbalance between anabolic and catabolic factors, the role of inflammatory mediators has long been neglected. However, past research clearly indicates that inflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α are expressed at higher levels in “diseased” intervertebral disks. Both disk cells as well as invading macrophages can be the source of the detected cytokines. Importantly, occurrence of inflammatory mediators in the disk can worsen the progress of degeneration by inducing the expression of matrix degrading enzymes as well as by inhibiting extracellular matrix synthesis. In addition, inflammatory mediators play a crucial role in pain development during intervertebral disk herniation (i.e., sciatica) and disk degeneration (i.e., discogenic pain). This review provides information on the most relevant inflammatory mediators during different types of disk diseases and explains how these factors can induce disk degeneration and the development of discogenic and sciatic/radiculopathic pain.

159 citations

Journal ArticleDOI
TL;DR: It is concluded that dynamic compression is consistent with a notion of “healthy” loading that is able to maintain or promote matrix biosynthesis without substantially disrupting disc structural integrity.

153 citations

Journal ArticleDOI
01 Aug 2008-Spine
TL;DR: IVD repair using MSCs requires increased knowledge of MSC response to the chemical microenvironment, and pH may be the major limitation for MSC-based IVD repair.
Abstract: Low back pain is the most common cause of activity limitation in people younger than 45 years and the second most frequent reason for visits to the physician. In addition, low back pain is the fifth-ranking cause of admission to the hospital, and the third most common cause of surgical procedures in the United States.1 Therefore, costs for the health care system due to low back pain is estimated to be 100 billion dollars.2 Low back pain is a multifactorial crisis, and intervertebral disc (IVD) degeneration plays an important role in its epidemiology.3-5 Recent approaches for biologic repair and regeneration of the IVD are under investigation including cell transplantation, administration of growth factors, and gene therapy.6,7 Mesenchymal stem cells (MSCs) may be ideal candidates for cell therapies and tissue engineering because of their high proliferation rate8 and potential for multilineage differentiation.9 The microenvironmental niche, characterized by the niche cells itself and their chemical and physical environment, has a strong influence on MSC behavior and differentiation.10 The harsh microenvironment of IVDs can influence resident cells negatively, and may be particularly critical for MSCs that might be implanted in the IVD. The response of MSCs to the microenvironmental conditions of the IVD under healthy and degeneration conditions is largely unknown, and it is not clear which factors, if any, are critical to successful MSC survival, proliferation, and differentiation. The IVD microenvironment has distinct and extreme chemical characteristics that are the focus of this study, including reduced nutrition, high extracellular osmolarity, and acidic pH. The response of IVD cells to microenvironmental conditions has been partially explored,11-20 but very few studies investigated MSCs in the IVD niche.21,22 Further, there is some evidence that the potential of MSCs may depend on the donor's age, although this has not been tested so far with regards to approaches for the IVD. Recent studies were able to show that their potential for differentiation and proliferation may be higher in younger donors compared with older donors.23-25 The aim of this study was to investigate effects of the chemical conditions representative of a healthy or mildly degenerated IVD on proliferation, viability, and gene expression of MSCs. We hypothesized certain IVD-like conditions will increase biosynthesis rates and proliferation whereas others will inhibit expression of important matrix proteins and also reduce MSC viability and proliferation. We also hypothesized MSCs harvested from young rats will be more adaptable to the IVD chemical niche than MSCs from mature rats.

145 citations


Cited by
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TL;DR: This text is a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA.
Abstract: The text consists of two sections, one for those studying or practicing diagnostic radiology, nuclear medicine and radiation oncology; the other for those engaged in the study or clinical practice of radiation oncology--a new chapter, on radiologic terrorism, is specifically for those in the radiation sciences who would manage exposed individuals in the event of a terrorist event. The 17 chapters in Section I represent a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA. The 11 chapters in Section II address more in-depth topics in radiation oncology, such as cancer biology, retreatment after radiotherapy, chemotherapeutic agents and hyperthermia.

1,359 citations

Journal ArticleDOI
TL;DR: An enhanced understanding of the contribution of cytokines and immune cells to these catabolic, angiogenic and nociceptive processes could provide new targets for the treatment of symptomatic disc disease.
Abstract: Degeneration of the intervertebral discs (IVDs) is a major contributor to back, neck and radicular pain. IVD degeneration is characterized by increases in levels of the proinflammatory cytokines TNF, IL-1α, IL-1β, IL-6 and IL-17 secreted by the IVD cells; these cytokines promote extracellular matrix degradation, chemokine production and changes in IVD cell phenotype. The resulting imbalance in catabolic and anabolic responses leads to the degeneration of IVD tissues, as well as disc herniation and radicular pain. The release of chemokines from degenerating discs promotes the infiltration and activation of immune cells, further amplifying the inflammatory cascade. Leukocyte migration into the IVD is accompanied by the appearance of microvasculature tissue and nerve fibres. Furthermore, neurogenic factors, generated by both disc and immune cells, induce expression of pain-associated cation channels in the dorsal root ganglion. Depolarization of these ion channels is likely to promote discogenic and radicular pain, and reinforce the cytokine-mediated degenerative cascade. Taken together, an enhanced understanding of the contribution of cytokines and immune cells to these catabolic, angiogenic and nociceptive processes could provide new targets for the treatment of symptomatic disc disease. In this Review, the role of key inflammatory cytokines during each of the individual phases of degenerative disc disease, as well as the outcomes of major clinical studies aimed at blocking cytokine function, are discussed.

1,053 citations

Journal ArticleDOI
TL;DR: It is argued that mechanics and biology are interconnected and amplify each other and the proposed disease model explains the comparable efficacy of very different animal models of disc degeneration, but also helps to consider the consequences of therapeutic interventions, either at the cellular, material or mechanical level.

528 citations

Journal ArticleDOI
TL;DR: It is suggested that genetic factors account for up to 75% of individual susceptibility to IVD degeneration, far more than the environmental factors such as occupational exposure or smoking that were previously suspected to figure prominently in this process.

401 citations

Journal ArticleDOI
TL;DR: A document that, since 2001, has provided a widely acceptable nomenclature that helps maintain consistency and accuracy in the description of the anatomic and physiologic properties of the normal and abnormal lumbar disc is revised and updated.

378 citations