Mechanotransduction via integrins and interleukinâ4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes

Millward-Sadler, S J; Wright, M O; Davies, Liza; Nuki, G; Salter, Donald

doi:10.1002/1529-0131(200009)43:9<2091::aid-anr21>3.0.co;2-c

Cited by 209 publications

(131 citation statements)

References 37 publications

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“…The control of MMP-3 expression in vivo is complex and not well understood, and could be subject to modulation by other transcription or post-transcription factors, such as cytokines (27,28); one of its polymorphisms is located within the interleukin-1 responsive element for several transcriptional regulators (29).…”

Section: A/6a Polymorphism Of Mmp-3mentioning

confidence: 99%

MMP-3 polymorphism: Genetic marker in pathological processes (Review)

2010

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Abstract. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are collectively capable of cleaving virtually all extracellular matrix (ecM) substrates and play an important role in diverse physiological and pathological processes. The activity of MMPs is controlled at multiple levels, and the transcriptional regulation of MMPs appears to represent a necessary step in its regulation. MMP-3 is a key member of the MMP family with broad substrate specificity, and is crucial to the connective tissue remodeling process. it is also involved in the turnover of the numerous ecM components. a common functional promoter polymorphism of MMP-3, 5a/6a, affects its activity and has been associated with various diseases. This polymorphism may be used as a genetic marker for certain pathologies to identify individual susceptibility. This review discusses various topics related to MMP-3 in pathological processes, with a focus on the 5a/6a polymorphism. Contents1. introduction 2. Matrix metalloproteinase-3 3. 5a/6a polymorphism of MMP-3 4. Pathological processes and the MMP-3 5a/6a polymorphism 5. Haplotype influence IntroductionThe evidence that individual characteristics play an important role in physiological and pathological processes has resulted in the targeted study of genetic polymorphisms in the clinical setting. in this context, mediators that degrade the extracellular matrix (ecM), such as matrix metalloproteinases (MMPs), are highlighted in studies involving inflammatory and degenerative diseases, and principally the prognosis and metastasis of cancer.degradation of the ecM is essential in many physiological processes, such as during development, growth and repair of tissue, and the microenvironment plays a central role in controlling both normal and transformed cell functions, as well as normal tissue integrity (1).MMPs are a pivotal family of zinc enzymes responsible for the degradation of ecM components, including basement membrane collagen, interstitial collagen, fibronectin and various proteoglycans, during normal remodeling and repair processes in development and inflammation. MMPs are also peptidase enzymes responsible for clotting factors, lipoproteins, latent growth factors and chemotactic and cell adhesion molecules (2,3). in this way, MMPs play a key role in the physiologic remodeling of tissues, including embryogenesis and tissue morphogenesis, angiogenesis, cell migration, proliferation, apoptosis, alteration of cell motility, effects on the immune system, wound repair and the inflammatory response (4).MMPs are a family of more than 25 enzymes. The expression of most MMPs is normally low in tissues and is induced when remodeling of the ecM is required. MMP gene expression is regulated primarily at the transcriptional level, but there is also evidence of the modulation of mrna stability in response to growth factors and cytokines (5). The promoter region of inducible MMP genes (i.e., MMP-3) shows remarkable conservation of regulatory elements, and their expression is induced ...

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Section: A/6a Polymorphism Of Mmp-3mentioning

confidence: 99%

MMP-3 polymorphism: Genetic marker in pathological processes (Review)

2010

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“…The initial inducers of cartilage catabolism in OA have not been identified. Potential stimuli include mechanical stress [50,51], and degradation products of ECM components including fibronectin fragments which stimulate production of matrix-degrading proteases [52][53][54][55]. IL-1 is a prototypical proinflammatory cytokine implicated in OA cartilage degradation which stimulates production of matrix metalloproteinases (MMPs).…”

Section: Cytokines Oxidative Damage and Chemokinesmentioning

confidence: 99%

“…Post-traumatic causes of OA Injurious and excessive mechanical stress can also result in depletion of proteoglycans and damage the collagen network [50,51]. Mechanical factors leading to joint damage can be viewed as factors that either compromise joint protection or excessively load the joint [76,77].…”

Section: 4mentioning

confidence: 99%

Cartilage tissue engineering for degenerative joint disease☆

Nešić

Whiteside

Brittberg

et al. 2006

Advanced Drug Delivery Reviews

210

156

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Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed.

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“…Millward-Sadler et al (22) applied hydrostatic pressure to chondrocyte monolayers at 0.33 Hz for 20 min in a manner that induced strain on the culture dish and plated cells (pressure-induced strain (PIS)). They observed an increase in aggrecan mRNA and a decrease in MMP-3 mRNA within 1 h following stimulation, with a return to base-line levels by 24 h. In a single experiment applying intermittent hydrostatic pressure to human chondrosarcoma cells, changes in the expression of 51 genes were measured by cDNA array technology without widespread change in RNA stability (23), indicating that many genes may be influenced by mechanical stimuli.…”

mentioning

confidence: 99%

“…Application of intermittent PIS to chondrocytes induced ␣ 5 ␤ 1 integrin activation of interleukin-4, which caused cell hyperpolarization via intracellular calcium release (24). Inhibition of interleukin-4 suppressed the up-regulation of aggrecan gene expression observed due to PIS (22). Intracellular calcium release, cAMP, and the phospholipase C pathway have been implicated for aggrecan gene up-regulation in response to static compression in cartilage explants (25).…”

mentioning

confidence: 99%

Mechanical Compression of Cartilage Explants Induces Multiple Time-dependent Gene Expression Patterns and Involves Intracellular Calcium and Cyclic AMP

Fitzgerald

Jin

Dean

et al. 2004

Journal of Biological Chemistry

223

184

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Chondrocytes are influenced by mechanical forces to remodel cartilage extracellular matrix. Previous studies have demonstrated the effects of mechanical forces on changes in biosynthesis and mRNA levels of particular extracellular matrix molecules, and have identified certain signaling pathways that may be involved. However, the broad extent and kinetics of mechano-regulation of gene transcription has not been studied in depth. We applied static compressive strains to bovine cartilage explants for periods between 1 and 24 h and measured the response of 28 genes using real time PCR. Compression time courses were also performed in the presence of an intracellular calcium chelator or an inhibitor of cyclic AMP-activated protein kinase A. Cluster analysis of the data revealed four main expression patterns: two groups containing either transiently up-regulated or duration-enhanced expression profiles could each be subdivided into genes that did or did not require intracellular calcium release and cyclic AMP-activated protein kinase A for their mechano-regulation. Transcription levels for aggrecan, type II collagen, and link protein were up-regulated ϳ2-3-fold during the first 8 h of 50% compression and subsequently down-regulated to levels below that of free-swelling controls by 24 h. Transcription levels of matrix metalloproteinases-3, -9, and -13, aggrecanase-1, and the matrix protease regulator cyclooxygenase-2 increased with the duration of 50% compression 2-16-fold by 24 h. Thus, transcription of proteins involved in matrix remodeling and catabolism dominated over anabolic matrix proteins as the duration of static compression increased. Immediate early genes c-fos and c-jun were dramatically up-regulated 6 -30-fold, respectively, during the first 8 h of 50% compression and remained up-regulated after 24 h. Articular cartilage is responsible for the smooth articulation of synovial joints during locomotion. Chondrocytes within cartilage constantly remodel the extracellular matrix (ECM) 1 of the tissue throughout life. The major load-bearing constituents of the ECM are type II collagen and aggregates of the proteoglycan, aggrecan, which provide the tensile and compressive stiffness of the tissue, respectively. Also present in the ECM are families of matrix proteinases, tissue inhibitors of matrix metalloproteinases (TIMPs), growth factors, and cytokines that together regulate ECM remodeling and turnover in health and disease (1). It is known that mechanical exercise of the knee joint in vivo increases the density of aggrecan in cartilage (2), whereas knee joint inactivity results in decreased aggrecan deposition (3, 4). Traumatic injury to cartilage diminishes mechanical strength and leads to excessive catabolism of the ECM, increasing the risk of osteoarthritis later in life (5).A number of model systems have been developed to simulate various aspects of the mechanical loading forces experienced by articular cartilage in vivo. Compressive and shear forces have been applied to cartilage explants and chondrocyte cul...

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Mechanotransduction via integrins and interleukinâ4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes

Cited by 209 publications

References 37 publications

MMP-3 polymorphism: Genetic marker in pathological processes (Review)

MMP-3 polymorphism: Genetic marker in pathological processes (Review)

Cartilage tissue engineering for degenerative joint disease☆

Mechanical Compression of Cartilage Explants Induces Multiple Time-dependent Gene Expression Patterns and Involves Intracellular Calcium and Cyclic AMP

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Mechanotransduction via integrins and interleukinâ4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes

Cited by 209 publications

References 37 publications

MMP-3 polymorphism: Genetic marker in pathological processes (Review)

MMP-3 polymorphism: Genetic marker in pathological processes (Review)

Cartilage tissue engineering for degenerative joint disease☆

Mechanical Compression of Cartilage Explants Induces Multiple Time-dependent Gene Expression Patterns and Involves Intracellular Calcium and Cyclic AMP

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Mechanotransduction via integrins and interleukinâ4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes