MT3-MMP (MMP-16) is Downregulated by<i>In Vitro</i>Cytokine Stimulation of Cartilage, but Unaltered in Naturally Occurring Equine Osteoarthritis and Osteochondrosis

Garvican, Elaine R.; Vaughan-Thomas, Anne; Redmond, C.; Clegg, Peter

doi:10.1080/03008200801913338

Cited by 12 publications

(7 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent upregulation of ADAMTS-5 expression in IL-1β-treated pellets in this study differs somewhat to the results by Little et al [13], where IL-1β-induced ADAMTS-5 expression was detected in metacarpophalangeal but not in carpal cartilage explants. However, our finding of increased MMP-13 expression after IL-1β treatment is in agreement with other equine studies [10][11][12][13][14][15]. In accordance with Little et al [13], who did not detect overall site-related differences in response to cytokine treatment (although individual variation was found), topographical differences in this study were only found for aggrecan expression after IL-1β treatment.…”

Section: Discussionsupporting

confidence: 94%

“…IL-1 has been shown to induce gene expression of matrix-degrading enzymes in equine chondrocytes [10][11][12][13][14][15], inhibition of proteoglycan synthesis [16][17][18][19], and increased release of glycosaminoglycans from cartilage explants [13,16,[19][20][21]. In addition, using cDNA array on equine monolayer chondrocytes, over 100 modulated transcripts were identified after brief exposure to IL-1β [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures

Ley

Svala

Nilton

et al. 2010

Connective Tissue Research

View full text Add to dashboard Cite

The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1β, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1β treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1β-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1β, whereas slight anabolic effects were induced by IL-6 and HMGB-1.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures

Ley

Svala

Nilton

et al. 2010

Connective Tissue Research

View full text Add to dashboard Cite

show abstract

“…In addition, gene expression is significantly downregulated by the addition of recombinant human interleukin-1b, oncostatin M, or tumor necrosis factor-a to normal cartilage explants (Garvican et al, 2008).…”

Section: Neoplastic Diseasesmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

View full text Add to dashboard Cite

a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

show abstract

“…Osteoarthritis (OA), also known as hypertrophic arthritis, is a degenerative joint disease and has become a prevalent clinical disorder in the elder [ 21 ]. Research has shown that many growth factors, cytokines and enzymes such as Interleukin (IL)-1β [ 22 ], metalloproteinases (MMPs) [ 23 ], inhibitors of metalloproteinase (TIMP)-1 [ 24 ] and collagenase [ 25 ] are closely related to the pathogenesis of OA. In addition, angiogenesis has been suggested to play important role in degeneration of articular cartilage after OA, and the level of vascular endothelial growth factor (VEGF) in OA cartilage is increased [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

The protective role of autophagy in experimental osteoarthritis, and the therapeutic effects of Torin 1 on osteoarthritis by activating autophagy

Cheng

Meng

2016

BMC Musculoskelet Disord

View full text Add to dashboard Cite

BackgroundRecent studies have shown that autophagy was associated with the development of osteoarthritis (OA), the purpose of this research was to determine the exact role of autophagy in OA and investigate effective therapeutic drugs to inhibit the pathological progression of OA.MethodsIn this study, a cellular OA model was generated by stimulating SW1353 cells with IL-1β and a rabbit OA model was established by intra-articular injection of collagenase, followed by treatment with Torin 1 or 3-Methyladenine (3-MA). The mRNA expression levels of VEGF, MMP-13 and TIMP-1 were determined by quantitative real-time PCR. The caitilage degeneration was examined by histological evaluation, chondrocytes degeneration and autophagosomes were observed by transmission electron microscopy. Expression levels of Beclin-1 and LC3 were evaluated by western blotting and immunofluorescence.ResultsThe degeneration of SW 1353 cells, cartilage and chondrocytes was related to the loss of autophagy in experimental OA. 3-MA increased the severity of degeneration of cells and cartilage by autophagy inhibition, while Torin 1 reduced that by autophagy activation.ConclusionsThe loss of autophagy is linked with the experimental OA and autophagy may play a protective role in the pathogenesis of OA. Treatment of Torin 1 can inhibit the degenerative changes of experimental OA by activating autophagy and it may be a useful therapeutic drug for OA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-0995-x) contains supplementary material, which is available to authorized users.

show abstract

MT3-MMP (MMP-16) is Downregulated byIn VitroCytokine Stimulation of Cartilage, but Unaltered in Naturally Occurring Equine Osteoarthritis and Osteochondrosis

Cited by 12 publications

References 54 publications

Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures

Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

The protective role of autophagy in experimental osteoarthritis, and the therapeutic effects of Torin 1 on osteoarthritis by activating autophagy

Contact Info

Product

Resources

About