Proteoglycan degradation by the ADAMTS family of proteinases

Stanton, Heather; Melrose, James; Little, Christopher B.; Fosang, Amanda J.

doi:10.1016/j.bbadis.2011.08.009

Cited by 172 publications

(158 citation statements)

References 182 publications

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“…Disintegrin sequences are also present in endogenous ligands such as the a disintegrin and metalloprotease (ADAM) family of metalloproteases (51). It is possible that a disintegrin may render the RGD motif inaccessible in OPN-R, and under such a circumstance, the C-ter- minal SVVYGLR may serve as an alternative cell-binding and cell-signaling motif (52,53).…”

Section: Discussionmentioning

confidence: 99%

Thrombin-cleaved Fragments of Osteopontin Are Overexpressed in Malignant Glial Tumors and Provide a Molecular Niche with Survival Advantage

Yamaguchi

Shao

Sharif

et al. 2013

Journal of Biological Chemistry

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Background: Osteopontin (OPN) is highly expressed in glioblastoma (GBM) and possesses inflammatory activity modulated by proteolytic cleavage. Results: Cleaved OPN was increased in GBM and led to more adhesion of GBM cells. OPN conferred resistance to apoptosis in GBM cells. Conclusion: Increased osteopontin proteolysis increased GBM cell resistance to apoptosis. Significance: OPN cleavage links coagulation and inflammation providing a favorable niche for GBM development.

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Section: Discussionmentioning

confidence: 99%

Thrombin-cleaved Fragments of Osteopontin Are Overexpressed in Malignant Glial Tumors and Provide a Molecular Niche with Survival Advantage

Yamaguchi

Shao

Sharif

et al. 2013

Journal of Biological Chemistry

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“…[86][87][88] The family of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteinases is another group of extracellular metalloproteinases with roles in ECM degradation. 89 Their ability to cleave procollagens and proteoglycans 89,90 suggests that they may influence on cardiac ECM integrity and function during heart failure progression. Interestingly, several members of the ADAMTS family were recently shown to be upregulated in pressureoverloaded hearts, 91 however the role of this family of proteinases in the diseased heart remains to be elucidated.…”

Section: Fibrosismentioning

confidence: 99%

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

et al. 2013

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Sustained pressure overload induces heart failure, the main cause of mortality in the Western world. Increased understanding of the underlying molecular mechanisms is essential to improve heart failure treatment. Despite important functions in other tissues, cardiac proteoglycans have received little attention. Syndecan‐4, a transmembrane heparan sulfate proteoglycan, is essential for pathological remodeling, and we here investigated its expression and shedding during heart failure. Pressure overload induced by aortic banding for 24 h and 1 week in mice increased syndecan‐4 mRNA, which correlated with mRNA of inflammatory cytokines. In cardiac myocytes and fibroblasts, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide through the toll‐like receptor‐4, induced syndecan‐4 mRNA. Bioinformatical and mutational analyses in HEK293 cells identified a functional site for the proinflammatory nuclear factor‐κB transcription factor in the syndecan‐4 promoter, and nuclear factor‐κB regulated syndecan‐4 mRNA in cardiac cells. Interestingly, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide induced nuclear factor‐κB‐dependent shedding of the syndecan‐4 ectodomain from cardiac cells. Overexpression of syndecan‐4 with mutated enzyme‐interacting domains suggested enzyme‐dependent heparan sulfate chains to regulate shedding. In cardiac fibroblasts, lipopolysaccharide reduced focal adhesion assembly, shown by immunohistochemistry, suggesting that inflammation‐induced shedding affects function. After aortic banding, a time‐dependent cardiac recruitment of T lymphocytes was observed by measuring CD3, CD4 and CD8 mRNA, which was reduced in syndecan‐4 knockout hearts. Finally, syndecan‐4 mRNA and shedding were upregulated in failing human hearts. Conclusively, our data suggest that syndecan‐4 plays an important role in the immune response of the heart to increased pressure, influencing cardiac remodeling and failure progression.

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“…It is proposed that aggrecan is degraded in the early stage of arthritis and is followed by collagen degradation. This earlier aggrecan depletion is thought to be due to the action of aggrecanases belonging to ADAMTSs family including ADAMTS-4 and -5 (Murphy and Nagase, 2008;Stanton et al, 2011). Indeed, cartilage matrix of ADAMTS-5 null mice was shown to be largely protected from challenges against antigen-induced arthritis (Stanton et al, 2005) and a mouse osteoarthritis (OA) model has been induced by surgical destabilisation of knee joints (Glasson et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Detection of cartilage matrix degradation by autofluorescence lifetime

et al. 2013

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Cartilage is a vital organ to maintain joint function. Upon arthritis, proteolytic enzymes initiate degradation of cartilage extracellular matrix (ECM) resulting in eventual loss of joint function. However, there are only limited ways of noninvasively monitoring early chemical changes in cartilage matrix. Here we report that the autofluorescence decay profiles of cartilage tissue are significantly affected by proteolytic degradation of cartilage ECM and can be characterised by measurements of the autofluorescence lifetime (AFL). A compact multidimensional fluorometer coupled to a fibre-optic probe was developed for single point measurements of AFL and applied to cartilage that was treated with different proteinases. Upon treating cartilage with bacterial collagenase, trypsin or matrix metalloproteinase 1, a significant dose and time dependent decrease of AFL was observed. Our data suggest that AFL of cartilage tissue is a potential non-invasive readout to monitor cartilage matrix integrity that may contribute to future diagnosis of cartilage defects as well as monitoring the efficacy of anti-joint therapeutic agents.

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Proteoglycan degradation by the ADAMTS family of proteinases

Cited by 172 publications

References 182 publications

Thrombin-cleaved Fragments of Osteopontin Are Overexpressed in Malignant Glial Tumors and Provide a Molecular Niche with Survival Advantage

Thrombin-cleaved Fragments of Osteopontin Are Overexpressed in Malignant Glial Tumors and Provide a Molecular Niche with Survival Advantage

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

Detection of cartilage matrix degradation by autofluorescence lifetime

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