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Search results for: ADAMTS5 Antibody

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#35726537   2022/06/21 To Up

Inhibition of HMGB1 suppresses inflammation and catabolism in temporomandibular joint osteoarthritis via NF-κB signaling pathway.

HMGB1 is a highly conserved nuclear protein that is rapidly released into the extracellular environment during infection or tissue damage. In osteoarthritis, HMGB1 acts as a pro-inflammatory cytokine inducing a positive feedback loop for synovial inflammation and cartilage degradation. The aim of this study was to explore the role of HMGB1 in inflammation and catabolism of temporomandibular joint osteoarthritis (TMJOA) and whether inhibition of HMGB1 affects TMJOA. Human synovial fibroblasts were incubated with HMGB1, the expression of pro-inflammatory cytokines and catabolic mediators were measured by Western blot and ELISA. NF-κB signaling pathway involvement was studied by the NF-κB inhibitor and detected by Western blotting and immunofluorescence staining. TMJOA was induced by an injection of Complete Freund's adjuvant (CFA) into anterosuperior compartment of rat's joint. An anti-HMGB1 antibody was used to assess the effect to HMGB1 in the synovium and cartilage of the CFA-induced TMJOA rats by H&E, Safranin O, Masson trichrome staining, immunohistochemistry and immunofluorescence. HMGB1 markedly increased the production of MMP13, ADAMTS5, IL-1β and IL-6 through activating NF-κB signaling pathway in human synovial fibroblasts. In vivo, application of the HMGB1 neutralizing antibody effectively ameliorated the detrimental extent of TMJOA. Furthermore, the HMGB1 neutralizing antibody reduced the expression of NF-κB, pro-inflammatory cytokines and catabolic mediators in the synovium and cartilage of CFA-induced TMJOA rats. HMGB1 inhibition alleviates TMJOA by reducing synovial inflammation and cartilage catabolism possibly through suppressing the NF-κB signaling pathway and may become a therapeutic method against TMJOA.
Yan Yan Li, Ya Ping Feng, Li Liu, Jin Ke, Xing Long

1588 related Products with: Inhibition of HMGB1 suppresses inflammation and catabolism in temporomandibular joint osteoarthritis via NF-κB signaling pathway.

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#34434966   2021/08/09 To Up

ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies.

ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathophysiological and molecular mechanisms underlying articular inflammation and mechanotransduction, as well as chondrocyte hypertrophy were discussed, and the role of ADAMTS5 in each biological process was reviewed, respectively. Senescence, inheritance, inflammation, and mechanical stress are involved in the overactivation of ADAMTS5, contributing to the pathogenesis of OA. Multiple molecular signaling pathways were observed to modulate ADAMTS5 expression, namely, Runx2, Fgf2, Notch, Wnt, NF-κB, YAP/TAZ, and the other inflammatory signaling pathways. Based on the fundamental understanding of ADAMTS5 in OA pathogenesis, monoclonal antibodies and small molecule inhibitors against ADAMTS5 were developed and proved to be beneficial pre-clinically both and . Recent novel RNA therapies demonstrated potentials in OA animal models. To sum up, ADAMTS5 inhibition and its signaling pathway-based modulations showed great potential in future therapeutic strategies for OA.
Lejian Jiang, Jiachen Lin, Sen Zhao, Jiaqian Wu, Yongming Jin, Li Yu, Nan Wu, Zhihong Wu, Yue Wang, Mao Lin

1935 related Products with: ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies.

100 5 mg100 μg 100 G500100 μg100ug Lyophilized100ug Lyophilized100 μg1001 Set

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#32825512   2020/08/20 To Up

The Anti-ADAMTS-5 Nanobody M6495 Protects Cartilage Degradation Ex Vivo.

Osteoarthritis (OA) is associated with cartilage breakdown, brought about by ADAMTS-5 mediated aggrecan degradation followed by MMP-derived aggrecan and type II collagen degradation. We investigated a novel anti-ADAMTS-5 inhibiting Nanobody (M6495) on cartilage turnover ex vivo. Bovine cartilage (BEX, = 4), human osteoarthritic - (HEX, = 8) and healthy-cartilage (hHEX, = 1) explants and bovine synovium and cartilage were cultured up to 21 days in medium alone (/), with pro-inflammatory cytokines (oncostatin M (10 ng/mL) + TNFα (20 ng/mL) (O + T), IL-1α (10 ng/mL) or oncostatin M (50 ng/mL) + IL-1β (10 ng/mL)) with or without M6495 (1000-0.46 nM). Cartilage turnover was assessed in conditioned medium by GAG (glycosaminoglycan) and biomarkers of ADAMTS-5 driven aggrecan degradation (huARGS and exAGNxI) and type II collagen degradation (C2M) and formation (PRO-C2). HuARGS, exAGNxI and GAG peaked within the first culture week in pro-inflammatory stimulated explants. C2M peaked from day 14 by O + T and day 21 in co-culture experiments. M6495 dose dependently decreased huARGS, exAGNxI and GAG after pro-inflammatory stimulation. In HEX C2M was dose-dependently reduced by M6495. M6495 showed no effect on PRO-C2. M6495 showed cartilage protective effects by dose-dependently inhibiting ADAMTS-5 mediated cartilage degradation and inhibiting overall cartilage deterioration in ex vivo cartilage cultures.
Anne Sofie Siebuhr, Daniela Werkmann, Anne-C Bay-Jensen, Christian S Thudium, Morten Asser Karsdal, Benedikte Serruys, Christoph Ladel, Martin Michaelis, Sven Lindemann

1842 related Products with: The Anti-ADAMTS-5 Nanobody M6495 Protects Cartilage Degradation Ex Vivo.

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#32156081   2020/03/07 To Up

Treatment of Dystrophic Mice with an ADAMTS-5 Specific Monoclonal Antibody Increases the Ex Vivo Strength of Isolated Fast Twitch Hindlimb Muscles.

Aberrant extracellular matrix synthesis and remodeling contributes to muscle degeneration and weakness in Duchenne muscular dystrophy (DMD). ADAMTS-5, a secreted metalloproteinase with catalytic activity against versican, is implicated in myogenesis and inflammation. Here, using the mouse model of DMD, we report increased ADAMTS-5 expression in dystrophic hindlimb muscles, localized to regions of regeneration and inflammation. To investigate the pathophysiological significance of this, 4-week-old mice were treated with an ADAMTS-5 monoclonal antibody (mAb) or IgG2c (IgG) isotype control for 3 weeks. ADAMTS-5 mAb treatment did not reduce versican processing, as protein levels of the cleaved versikine fragment did not differ between hindlimb muscles from ADAMTS-5 mAb or IgG treated mice. Nonetheless, ADAMTS-5 blockade improved ex vivo strength of isolated fast , but not slow , muscles. The underpinning mechanism may include modulation of regenerative myogenesis, as ADAMTS-5 blockade reduced the number of recently repaired desmin positive myofibers without affecting the number of desmin positive muscle progenitor cells. Treatment with the ADAMTS-5 mAb did not significantly affect makers of muscle damage, inflammation, nor fiber size. Altogether, the positive effects of ADAMTS-5 blockade in dystrophic muscles are fiber-type-specific and independent of versican processing.
Alex B Addinsall, Leonard G Forgan, Natasha L McRae, Rhys W Kelly, Penny L McDonald, Bryony McNeill, Daniel R McCulloch, Nicole Stupka

1894 related Products with: Treatment of Dystrophic Mice with an ADAMTS-5 Specific Monoclonal Antibody Increases the Ex Vivo Strength of Isolated Fast Twitch Hindlimb Muscles.

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#31734268   2019/11/14 To Up

Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.

Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction.
N Sharma, P Drobinski, A Kayed, Z Chen, C F Kjelgaard-Petersen, T Gantzel, M A Karsdal, M Michaelis, C Ladel, A C Bay-Jensen, S Lindemann, C S Thudium

1530 related Products with: Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.

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#31366218   2019/08/01 To Up

Mice Exhibit Altered Aggrecan Proteolytic Profiles That Correlate With Ascending Aortic Anomalies.

Investigate the requirement of Aggrecan (Acan) cleavage during aortic wall development in a murine model with ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin-type motifs) 5 deficiency and bicuspid aortic valves.
Loren E Dupuis, E Lockett Nelson, Brittany Hozik, Sarah C Porto, Alexandra Rogers-DeCotes, Amanda Fosang, Christine B Kern

1103 related Products with: Mice Exhibit Altered Aggrecan Proteolytic Profiles That Correlate With Ascending Aortic Anomalies.

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#29718273   // To Up

FGF23 Regulates Wnt/β-Catenin Signaling-Mediated Osteoarthritis in Mice Overexpressing High-Molecular-Weight FGF2.

Although humans with X-linked hypophosphatemia (XLH) and the Hyp mouse, a murine homolog of XLH, are known to develop degenerative joint disease, the exact mechanism that drives the osteoarthritis (OA) phenotype remains unclear. Mice that overexpress high-molecular-weight fibroblast growth factor (FGF) 2 isoforms (HMWTg mice) phenocopy both XLH and Hyp, including OA with increased FGF23 production in bone and serum. Because HMWTg cartilage also has increased FGF23 and there is cross-talk between FGF23-Wnt/β-catenin signaling, the purpose of this study was to determine if OA observed in HMWTg mice is due to FGF23-mediated canonical Wnt signaling in chondrocytes, given that both pathways are implicated in OA pathogenesis. HMWTg OA joints had decreased Dkk1, Sost, and Lrp6 expression with increased Wnt5a, Wnt7b, Lrp5, Axin2, phospho-GSK3β, Lef1, and nuclear β-catenin, as indicated by immunohistochemistry or quantitative PCR analysis. Chondrocytes from HMWTg mice had enhanced alcian blue and alkaline phosphatase staining as well as increased FGF23, Adamts5, Il-1β, Wnt7b, Wnt16, and Wisp1 gene expression and phospho-GSK3β protein expression as indicated by Western blot, compared with chondrocytes of vector control and chondrocytes from mice overexpressing the low-molecular-weight isoform, which were protected from OA. Canonical Wnt inhibitor treatment rescued some of those parameters in HMWTg chondrocytes, seemingly delaying the initially accelerated chondrogenic differentiation. FGF23 neutralizing antibody treatment was able to partly ameliorate OA abnormalities in subchondral bone and reduce degradative/hypertrophic chondrogenic marker expression in HMWTg joints in vivo. These results demonstrate that osteoarthropathy of HMWTg is at least partially due to FGF23-modulated Wnt/β-catenin signaling in chondrocytes.
Patience Meo Burt, Liping Xiao, Marja M Hurley

2427 related Products with: FGF23 Regulates Wnt/β-Catenin Signaling-Mediated Osteoarthritis in Mice Overexpressing High-Molecular-Weight FGF2.

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#29515038   2018/03/08 To Up

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.
Frank S Cikach, Christopher D Koch, Timothy J Mead, Josephine Galatioto, Belinda B Willard, Kelly B Emerton, Matthew J Eagleton, Eugene H Blackstone, Francesco Ramirez, Eric E Roselli, Suneel S Apte

1273 related Products with: Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

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#29137610   2017/11/14 To Up

Hemoglobin stimulates the expression of ADAMTS-5 and ADAMTS-9 by synovial cells: a possible cause of articular cartilage damage after intra-articular hemorrhage.

ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteins play an important pathological role in matrix degeneration. Aggrecan degradation is a significant and critical event in early-stage osteoarthritis. To determine the effect of hemoglobin (Hb) on the ability of synovial tissues to produce ADAMTS family members, we examined the influence of Hb by synovial cells in an in vitro experimental system.
Takuya Tajima, Tomohisa Sekimoto, Nami Yamaguchi, Noboru Taniguchi, Syuji Kurogi, Masugi Maruyama, Etsuo Chosa

2399 related Products with: Hemoglobin stimulates the expression of ADAMTS-5 and ADAMTS-9 by synovial cells: a possible cause of articular cartilage damage after intra-articular hemorrhage.

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