Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA

Lai, Yongjie; Yu, Xiuping; Zhang, Y.; Tian, Qingyun; Song, Hyun Jin; Mucignat, Maria Teresa; Perris, Roberto; Samuels, Jonathan; Krasnokutsky, Svetlana; Attur, Mukundan; Greenberg, Jeffrey D.; Abramson, Steven B.; Cesare, Paul E. Di; Liu, Chuanju

doi:10.1016/j.joca.2012.05.003

Cited by 36 publications

(48 citation statements)

References 37 publications

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“…Characteristics of these COMP fragments have previously been described using mouse monoclonal epitope mapping (32,33). However, the present report for the first time defines ending amino acids, neoepitopes, within these COMP fragments.…”

Section: Discussionmentioning

confidence: 70%

Novel Cartilage Oligomeric Matrix Protein (COMP) Neoepitopes Identified in Synovial Fluids from Patients with Joint Diseases Using Affinity Chromatography and Mass Spectrometry

Åhrman

Lorenzo

Holmgren

et al. 2014

Journal of Biological Chemistry

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Background: To understand molecular processes underlying cartilage destruction, we analyzed COMP fragments released into synovial fluid in joint diseases. Results: Twelve novel COMP neoepitopes have been identified. Conclusion:The release of COMP neoepitopes provides means for monitoring disease progression. Significance: Based on the specificity, selectivity, and sensitivity of each neoepitope, a new generation of biomarkers for cartilage destruction can be developed.

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Section: Discussionmentioning

confidence: 70%

Novel Cartilage Oligomeric Matrix Protein (COMP) Neoepitopes Identified in Synovial Fluids from Patients with Joint Diseases Using Affinity Chromatography and Mass Spectrometry

Åhrman

Lorenzo

Holmgren

et al. 2014

Journal of Biological Chemistry

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“…In this study, we generated a DMM model in WT and PGRN−/− mice, and PGRN−/− mice exhibited exaggerated progression of OA following induction of DMM. More severe loss of proteoglycan in Safranin O staining, significantly higher arthritis score based on histology, the elevated expression of Col X36 and MMP13,32 33 as well as more degraded COMP fragments20 were observed in the PGRN−/− group. An ACLT mice model37–40 was also chosen and treated by intra-articular injection with recombinant PGRN.…”

Section: Discussionmentioning

confidence: 91%

“…COMP is known to be a critical extracellular matrix protein of cartilage. We have previously demonstrated that COMP fragmentation implies severity of cartilage degradation, and hace designed a novel ELISA for circulating COMP fragment level 20. In this study, sera were collected from both genotypes at indicated time points following DMM operation and assayed through COMP fragment-specific ELISA.…”

Section: Resultsmentioning

confidence: 99%

Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling

et al. 2014

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Objective Progranulin (PGRN) was previously isolated as an osteoarthritis (OA)-associated growth factor. Additionally, PGRN was found to play a therapeutic role in inflammatory arthritis mice models through antagonising tumour necrosis factor α (TNF-α). This study was aimed at investigating the role of PGRN in degradation of cartilage and progression of OA. Methods Progression of OA was analysed in both spontaneous and surgically induced OA models in wild type and PGRN-deficient mice. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry and ELISA. Additionally, mRNA expression of degenerative factors and catabolic markers known to be involved in cartilage degeneration in OA were analysed. Furthermore, the anabolic effects and underlying mechanisms of PGRN were investigated by in vitro experiments with primary chondrocytes. Results Here, we found that deficiency of PGRN led to spontaneous OA-like phenotype in `aged' mice. Additionally, PGRN-deficient mice exhibited exaggerated breakdown of cartilage structure and OA progression, while local delivery of recombinant PGRN protein attenuated degradation of cartilage matrix and protected against OA development in surgically induced OA models. Furthermore, PGRN activated extracellular signal-regulated kinases (ERK) 1/2 signalling and elevated the levels of anabolic biomarkers in human chondrocyte, and the protective function of PGRN was mediated mainly through TNF receptor 2. Additionally, PGRN suppressed inflammatory action of TNF-α and inhibited the activation of β-Catenin signalling in cartilage and chondrocytes. Conclusions Collectively, this study provides new insight into the pathogenesis of OA, and also presents PGRN as a potential target for the treatment of joint degenerative diseases, including OA.

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“…Serum concentration of COMP was analysed by our new sandwich ELISA 21. The detailed method for this ELISA is available in online supplementary materials and methods.…”

Section: Methodsmentioning

confidence: 99%

ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis

et al. 2013

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Objective To examine the expression of ADAMTS-7 during the progression of osteoarthritis (OA), defining its role in the pathogenesis of OA, and elucidating the molecular events involved. Methods ADAMTS-7 expression in cartilage of a rat OA model was assayed using immunohistochemistry. Cartilage-specific ADAMTS-7 transgenic mice and ADAMTS-7 small interfering (si)RNA knockdown mice were generated and used to analyse OA progression in both spontaneous and surgically induced OA models. Cartilage degradation and OA was evaluated using Safranin-O staining, immunohistochemistry, ELISA and western blotting. In addition, mRNA expression of tumour necrosis factor (TNF)-α and metalloproteinases known to be involved in cartilage degeneration in OA was analysed. Furthermore, the transactivation of ADAMTS-7 by TNF-α and its downstream NF-κB signalling was measured using reporter gene assay. Results ADAMTS-7 expression was elevated during disease progression in the surgically induced rat OA model. Targeted overexpression of ADAMTS-7 in chondrocytes led to chondrodysplasia characterised by short-limbed dwarfism and a delay in endochondral ossification in ‘young mice’ and a spontaneous OA-like phenotype in ‘aged’ mice. In addition, overexpression of ADAMTS-7 led to exaggerated breakdown of cartilage and accelerated OA progression, while knockdown of ADAMTS-7 attenuated degradation of cartilage matrix and protected against OA development, in surgically induced OA models. ADAMTS-7 upregulated TNF-α and metalloproteinases associated with OA; in addition, TNF-α induced ADAMTS-7 through NF-κB signalling. Conclusions ADAMTS-7 and TNF-α form a positive feedback loop in the regulation of cartilage degradation and OA progression, making them potential molecular targets for prevention and treatment of joint degenerative diseases, including OA.

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Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA

Cited by 36 publications

References 37 publications

Novel Cartilage Oligomeric Matrix Protein (COMP) Neoepitopes Identified in Synovial Fluids from Patients with Joint Diseases Using Affinity Chromatography and Mass Spectrometry

Novel Cartilage Oligomeric Matrix Protein (COMP) Neoepitopes Identified in Synovial Fluids from Patients with Joint Diseases Using Affinity Chromatography and Mass Spectrometry

Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling

ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis

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