scholarly journals Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model

2010 ◽  
Vol 12 (6) ◽  
pp. R224 ◽  
Author(s):  
Samuel García ◽  
Jerónimo Forteza ◽  
Carlos López-Otin ◽  
Juan J Gómez-Reino ◽  
Antonio González ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Bone Erosion ◽  
Joint Inflammation ◽  
Arthritis Model ◽  
Serum Transfer

scholarly journals OP0182 PROTEOGLYCAN LOSS IN ARTICULAR CARTILAGE IS ASSOCIATED WITH JOINT INFLAMMATION SEVERITY IN PSORIATIC ARTHRITIS – A COMPOSITIONAL MAGNETIC RESONANCE IMAGING STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 113.2-113
Author(s):  
P. Sewerin ◽  
D. Abrar ◽  
S. Nebelung ◽  
M. Frenken ◽  
T. Ulrich ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Bone Erosion ◽  
Joint Inflammation ◽  
Resonance Imaging ◽  
Research Support ◽  
Weighted Image ◽  
The Third ◽  
Deutschland Gmbh ◽  
Pip Joint ◽  
Flexor Tenosynovitis

Background:Even though cartilage loss is a known feature of psoriatic arthritis (PsA), little is known about its role in the pathogenesis of PsA. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) as a non-invasive marker of the tissue’s proteoglycan content, such early (i.e. pre-morphological) changes have been associated with inflammation in rheumatoid arthritis (RA). Yet, this association has not been studied before in PsA.Objectives:Is the severity of local joint inflammation associated to local proteoglycan loss in PsA patients?Methods:Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution clinical standard morphological and dGEMRIC sequences using a 3T MRI scanner (Magnetom Skyra, Siemens) and a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS) and total cartilage thickness (TCT). Kendall-Tau correlation coefficients (τ) were calculated.Results:We found significant negative correlations between dGEMRIC indices and total PsAMRIS (τ = -0.5, p= 0.012), synovitis (τ = -0.56, p= 0.006), flexor tenosynovitis (τ = -0.4, p= 0.049), and periarticular inflammation (τ = -0.72, p< 0.001). Significant positive correlations were found between TCT and dGEMRIC indices in all joint levels (τ = 0.43, p<0.001). No significant correlations were determined between dGEMRIC indices and bone erosion, bone edema or bone proliferation.Conclusion:In PsA, proteoglycan loss as assessed by dGEMRIC is associated with periarticular inflammation, synovitis, and flexor tenosynovitis, but not with bone erosion or proliferation, thereby highlighting the need for effective anti-inflammatory treatment regimes. Beyond morphology, advanced MRI techniques may be used to assess cartilage composition in PsA and to identify early changes in cartilage as an imaging biomarker with potential application in detection and monitoring of PsA.Figure 1Right hand of a 26-year-old male with psoriatic arthritis Coronal STIR image (A) of digits 1-5, transversal fat-saturated (fs) T2-weighted image of digits 2-4 (B) and the corresponding transversal fs contrast-enhanced T1-weighted image (C) at the distal portion of the proximal phalanges. Horizontal white bar in (A) indicates level of transversal slices (B) & (C). Sagittal fs Proton Density-weighted image of the third digit (D). A: Increased signal at the collateral ligaments and synovitis of the proximal interphalangeal (PIP) joint of the third digit (white arrow). Periarticular inflammation around the PIP joint and the body of the proximal phalanx of the third digit (arrowhead). B & C: Extensive flexor tenosynovitis (asterix) and periarticular inflammation in the subcutaneous tissues (arrowhead) alongside thickened flexor tendon pulleys (arrow). D & E: Representative sagittal T1-weighted images of the MCP, PIP and DIP joint of the 3rd digit. Following iv contrast administration and appropriate delay of 40 min, A gives the morphological T1 map, while B gives the corresponding parameter map with dGEMRIC values [ms] overlaid. Note the significant decrease in dGEMRIC indices of the PIP joint as compared to the MCP joint.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Daniel Abrar: None declared, Sven Nebelung: None declared, Miriam Frenken: None declared, Tim Ulrich: None declared, Karl Ludger Radke: None declared, Gerald Antoch: None declared, Stefan Vordenbäumen: None declared, Ralph Brinks: None declared, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Benedikt Ostendorf: None declared, Christoph Schleich: None declared

Evaluation of inflammatory change and bone erosion using a murine type II collagen-induced arthritis model

2010 ◽  
Vol 31 (5) ◽  
pp. 595-603 ◽  
Author(s):  
Samjin Choi ◽  
Yeon-Ah Lee ◽  
Seung-Jae Hong ◽  
Gi-Ja Lee ◽  
Sung Wook Kang ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Type Ii Collagen ◽  
Inflammatory Change ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Arthritis Model

The CO-releasing molecule CORM-3 protects against articular degradation in the K/BxN serum transfer arthritis model

2010 ◽  
Vol 634 (1-3) ◽  
pp. 184-191 ◽  
Author(s):  
Nuria Maicas ◽  
Maria Luisa Ferrándiz ◽  
Isabel Devesa ◽  
Roberto Motterlini ◽  
Marije I. Koenders ◽  
...  
Keyword(s):  
Arthritis Model ◽  
Serum Transfer

scholarly journals A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Louie C. Alexander ◽  
Grant McHorse ◽  
Janet L. Huebner ◽  
Anne-Christine Bay-Jensen ◽  
Morten A. Karsdal ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Joint Inflammation ◽  
Cartilage Degradation ◽  
Womac Pain ◽  
Type Iii Collagen ◽  
Type I ◽  
Radiographic Imaging ◽  
Type Iii

Abstract Objective To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. Methods Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). Results BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. Conclusions To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

scholarly journals ZhiJingSan Inhibits Osteoclastogenesis via Regulating RANKL/NF-κB Signaling Pathway and Ameliorates Bone Erosion in Collagen-Induced Mouse Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanyuan Ling ◽  
Jie Yang ◽  
Di Hua ◽  
Dawei Wang ◽  
Chenglei Zhao ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Bone Erosion ◽  
Cell Model ◽  
Pathological Condition ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Joint Inflammation ◽  
Underlying Mechanism ◽  
Bovine Collagen

Bone erosion is the most evident pathological condition of rheumatoid arthritis (RA), which is the main cause of joint deformities and disability in RA patients. At present, the conventional RA drugs have not achieved satisfactory effect in improving bone erosion. ZhiJingSan (ZJS), which is a traditional Chinese prescription composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch, scolopendridae) and scorpion (dried body of Buthus martensii Karsch, Buthus), exhibits anti-rheumatism, analgesic and joint deformities improvement effects. This study aimed to assess the therapeutic effect of ZJS on RA bone erosion and to elucidate the underlying mechanism. The effect of ZJS on RA bone erosion was investigated in a murine model of bovine collagen-induced arthritis (CIA), and the underlying mechanism was investigated in vitro in an osteoclast differentiation cell model. Administration of ZJS delayed the onset of arthritis, alleviated joint inflammation, and attenuated bone erosion in the CIA mice. Meanwhile, ZJS decreased the serum levels of TNF-α, IL-6, and anti-bovine collagen II-specific antibodies. Furthermore, ZJS treatment reduced the number of osteoclasts and the expression of cathepsin K in the ankle joints of CIA mice. ZJS also inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of MMP9 and cathepsin K in vitro. Mechanistically, ZJS blocked RANKL-induced p65 phosphorylation, nucleation, and inhibited the expression of downstream NFATc1 and c-Fos in bone marrow-derived macrophages (BMMs). Taken together, ZJS exerts a therapeutic effect on bone erosion in CIA mice by inhibiting RANKL/NF-κB-mediated osteoclast differentiation, which suggested that ZJS is a promising prescription for treating RA bone erosion.

Matrix Metalloproteinase-3 induces proteoglycan degradation in gouty arthritis model

Gene ◽  
2021 ◽  
Vol 765 ◽  
pp. 145120
Author(s):  
Le Shi ◽  
Tao Liang ◽  
Fan Yang ◽  
Fang-Fang Zhu ◽  
Jin Liu ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Gouty Arthritis ◽  
Arthritis Model ◽  
Matrix Metalloproteinase 3 ◽  
Proteoglycan Degradation

IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion

2020 ◽  
Author(s):  
Sadiq Umar ◽  
Karol Palasiewicz ◽  
Katrien Van Raemdonck ◽  
Michael V. Volin ◽  
Bianca Romay ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Inflammation ◽  
Promising Strategy

scholarly journals TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding

2017 ◽  
Vol 52 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Amy J. Naylor ◽  
Guillaume Desanti ◽  
Atif N. Saghir ◽  
Rowan S. Hardy
Keyword(s):  
Animal Welfare ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Joint Inflammation ◽  
Micro Computed Tomography ◽  
Necrosis Factor Alpha ◽  
Clinical Scores ◽  
Breeding Management ◽  
Factor Alpha ◽  
Breeding Groups

Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNFΔARE mouse have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans. Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment to breeding management. We examined whether TNFα depleting therapy ‘infliximab’ might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNFΔARE males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection. Joint histology and bone morphology were assessed by histological analysis and micro-computed tomography (CT), respectively. Analysis of breeding was examined retrospectively in TNFΔARE males prior to, and following, regular introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNFΔARE males receiving infliximab (control 6.6 arbitrary units [AU] ± 0.88 versus infliximab 4.4 AU ± 1.4; P < 0.05), while measures of pannus invasion and bone erosion by histology and micro-CT were markedly reduced. In the breeding groups, TNFΔARE males receiving infliximab injections sired more litters over their breeding lifespan (control 1.69 ± 0.22 versus infliximab 3.00 ± 0.19; P < 0.005). Furthermore, prior to infliximab, TNFΔARE males had a 26% risk of failing to sire any litters. This was reduced to 7% after the introduction of infliximab. This study is the first to report that regular administration of infliximab is effective at suppressing disease activity and improving animal welfare in TNFΔARE animals. In addition, we have shown that infliximab is highly efficacious in improving breeding behaviour and increasing the number of litters sired by TNFΔARE males.

scholarly journals TRANCE/RANKL Knockout Mice Are Protected from Bone Erosion in a Serum Transfer Model of Arthritis

2001 ◽  
Vol 159 (5) ◽  
pp. 1689-1699 ◽  
Author(s):  
Allison R. Pettit ◽  
Hong Ji ◽  
Dietrich von Stechow ◽  
Ralph Müller ◽  
Steven R. Goldring ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Bone Erosion ◽  
Transfer Model ◽  
Serum Transfer ◽  
Serum Transfer Model

Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

2004 ◽  
Vol 50 (2) ◽  
pp. 650-659 ◽  
Author(s):  
Erik Lubberts ◽  
Marije I. Koenders ◽  
Birgitte Oppers-Walgreen ◽  
Liduine van den Bersselaar ◽  
Christina J. J. Coenen-de Roo ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Inflammation ◽  
Cartilage Destruction ◽  
Interleukin 17 ◽  
Collagen Induced Arthritis
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