MMPs and ADAMTSs in intervertebral disc degeneration

Wang, Wenjun; Yu, Xiaohua; Wang, Cheng; Yang, Wei; He, Wen-Si; Zhang, Shujun; Yan, Yongping; Zhang, Jian

doi:10.1016/j.cca.2015.06.023

Cited by 162 publications

(136 citation statements)

References 123 publications

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“…IL-1β and TNF-α are secreted by cells of the immune system, such as macrophages, and by a variety of other cells types, including chondrocytes, annulus fibrosus (AF) and nucleus pulposus (NP) cells, regulating host responses to stress, inflammation, infection or trauma (Berenbaum, 2013;Johnson et al, 2015;Oda et al, 2004;Vo et al, 2016). IL-1β and TNF-α are known to activate nuclear factor κB (NF-κB), c-Jun N-terminal protein kinase (JNK) and/ or p38 mitogen-activated protein kinase (MAPK) (Hoyland et al, 2008;McNulty et al, 2009;Vo et al, 2013;Wang et al, 2015;Wilusz et al, 2008). Activation of these kinases results in the transcription of inflammatory and catabolic genes, such as interleukins, collagenases [matrix metalloproteinases (MMPs)], aggrecanases (ADAMTS) and molecules that promote pain, including cyclooxygenase 2 (COX-2), nerve growth factor (NGF) and inducible nitric oxide synthase (iNOS) (Johnson et al, 2015;Ricciotti and FitzGerald, 2011;Vo et al, 2013;Wuertz and Haglund, 2013).…”

Section: Trpml2 -/-mentioning

confidence: 99%

The role of transient receptor potential channels in joint diseases

Krupková

Zvick²,

Wuertz‐Kozak³

2017

eCM

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Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous as well as exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca 2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation as well as activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells and the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.

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Section: Trpml2 -/-mentioning

confidence: 99%

The role of transient receptor potential channels in joint diseases

Krupková

Zvick²,

Wuertz‐Kozak³

2017

eCM

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“…Other, more minor, proteoglycans with specific roles to play in the composite IVD include members of the small leucine repeat proteoglycan (SLRP) family, decorin, biglycan, fibromodulin, lumican, and keratocan [12,13], the CS-hyalectan member, versican, the lubricative proteoglycan, lubricin, and the large modular HS/CS proteoglycan perlecan [14] (reviewed in [15]). With ageing and degeneration, proteoglycans are lost from the NP through proteolytic cleavage [16,17,18,19] and the IVD becomes progressively more dehydrated and less biomechanically competent [3]. The matrix metalloproteinases (MMPs) produced by disc cells are regulated by the mechanical microenvironment of the cells [17,18,20] and can predispose the IVD to further mechanical damage and the generation of a number of characteristic lesions primarily in the AF [21].…”

Section: Introductionmentioning

confidence: 99%

A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

Shu

Smith

et al. 2017

IJMS

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The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i–vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3–6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in carrier injected discs.

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“…In addition to the catabolic and pro-inflammatory effects, IL-1β and TNF-α can influence disc cell senescence, autophagy and the expression of genes involved in proliferation [13]. MMPs and aggrecanases further promote degradation of the extracellular matrix (ECM) [10,14,15]. Changes of the NP ultimately result in a loss of disc hydration, load-bearing capacity, and disc height at later stages [16,17].…”

Section: Introductionmentioning

confidence: 99%

An Inflammatory Nucleus Pulposus Tissue Culture Model to Test Molecular Regenerative Therapies: Validation with Epigallocatechin 3-Gallate

Krupková

Hlavna

Tahmasseb

et al. 2016

IJMS

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Organ cultures are practical tools to investigate regenerative strategies for the intervertebral disc. However, most existing organ culture systems induce severe tissue degradation with only limited representation of the in vivo processes. The objective of this study was to develop a space- and cost-efficient tissue culture model, which represents degenerative processes of the nucleus pulposus (NP). Intact bovine NPs were cultured in a previously developed system using Dyneema jackets. Degenerative changes in the NP tissue were induced either by the direct injection of chondroitinase ABC (1–20 U/mL) or by the diffusion of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) (both 100 ng/mL) from the culture media. Extracellular matrix composition (collagens, proteoglycans, water, and DNA) and the expression of inflammatory and catabolic genes were analyzed. The anti-inflammatory and anti-catabolic compound epigallocatechin 3-gallate (EGCG, 10 µM) was employed to assess the relevance of the degenerative NP model. Although a single injection of chondroitinase ABC reduced the proteoglycan content in the NPs, it did not activate cellular responses. On the other hand, IL-1β and TNF-α significantly increased the mRNA expression of inflammatory mediators IL-6, IL-8, inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinases (MMP1, MMP3, and MMP13). The cytokine-induced gene expression in the NPs was ameliorated with EGCG. This study provides a proof of concept that inflammatory NP cultures, with appropriate containment, can be useful for the discovery and evaluation of molecular therapeutic strategies against early degenerative disc disease.

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MMPs and ADAMTSs in intervertebral disc degeneration

Cited by 162 publications

References 123 publications

The role of transient receptor potential channels in joint diseases

The role of transient receptor potential channels in joint diseases

A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

An Inflammatory Nucleus Pulposus Tissue Culture Model to Test Molecular Regenerative Therapies: Validation with Epigallocatechin 3-Gallate

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