Degradation in vivo of articular cartilage in rheumatoid arthritis and juvenile chronic arthritis by cathepsin G and elastase from polymorphonuclear leukocytes

1987 ◽  
Vol 7 (5) ◽  
pp. 195-202 ◽  
Author(s):  
M. Velvart ◽  
K. Fehr
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Cartilage ◽  
Polymorphonuclear Leukocytes ◽  
Juvenile Chronic Arthritis ◽  
Chronic Arthritis ◽  
Cathepsin G

Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

1992 ◽  
Vol 67 (06) ◽  
pp. 660-664 ◽  
Author(s):  
Virgilio Evangelista ◽  
Paola Piccardoni ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Platelet Activation ◽  
Polymorphonuclear Leukocytes ◽  
Direct Interaction ◽  
Cathepsin G ◽  
In Vivo Test ◽  
Cell Functions ◽  
Test Models ◽  
Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

scholarly journals Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 902
Author(s):  
Susanne N. Wijesinghe ◽  
Mark A. Lindsay ◽  
Simon W. Jones
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Cartilage ◽  
Joint Diseases ◽  
Synovial Joint ◽  
Pharmacological Treatments ◽  
In Vivo Models ◽  
Inflammatory Joint Diseases ◽  
Joint Pathology ◽  
Cellular Pathways

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

scholarly journals Cathepsin G-dependent platelet stimulation by activated polymorphonuclear leukocytes and its inhibition by antiproteinases: role of P-selectin-mediated cell-cell adhesion

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2947-2957 ◽  
Author(s):  
V Evangelista ◽  
P Piccardoni ◽  
JG White ◽  
G de Gaetano ◽  
C Cerletti
Keyword(s):  
Functional Role ◽  
Polymorphonuclear Leukocytes ◽  
Platelet Adhesion ◽  
Inhibitory Effect ◽  
Serotonin Release ◽  
Cathepsin G ◽  
Inhibitory Antibody ◽  
Neuraminidase Treatment

Human PMN stimulated by fMLP are able to activate coincubated, autologous platelets. Cathepsin G, a neutral serine protease stored in the azurophilic granules of PMN, is the major platelet activator in this system. We previously proposed that shear-induced close PMN- platelet contact creates the conditions for which cathepsin G activity on platelets is protected against antiproteinases. The aim of this study was to investigate the adhesive mechanisms, possibly creating between PMN and platelet membranes the microenvironment in which cathepsin G, discharged from stimulated PMN onto adherent platelets, is protected against antiproteinases. Microscopic examination showed that under conditions of high shear, 71.3% +/- 6.1% of PMN were associated to platelets forming small clumps. This percentage decreased to 10% +/- 2% and 13% +/- 4%, respectively, in the presence of an inhibitory antibody to P-selectin or 20 mmol/L mannose-1-phosphate and to 10.8% +/- 3.7% when cells were not stirred. Similarly, PMN pretreatment with neuraminidase abolished PMN binding to platelets. These results indicate that P-selectin mediates PMN-platelet adhesion occurring before PMN stimulation. Prevention of PMN-platelet contact significantly potentiated the inhibitory effect of alpha 1-protease inhibitor on subsequent cathepsin G-induced platelet serotonin release. Because anti-P-selectin antibody, mannose-1-phosphate, and neuraminidase treatment of PMN did not modify PMN-induced platelet activation in the absence of antiproteinases, it is suggested that P- selectin-mediated PMN-platelet adhesion results in the formation of a sequestered microenvironment between cell membranes, in which higher amounts of antiproteinases are required to prevent the activity of released cathepsin G. These data add a new functional role to P- selectin-mediated PMN-platelet adhesion that could be important in vivo because of the presence of antiproteinases in plasma.

scholarly journals Anti-tumor necrosis factor α switching in rheumatoid arthritis and juvenile chronic arthritis

2004 ◽  
Vol 51 (2) ◽  
pp. 301-302 ◽  
Author(s):  
Ennio Giulio Favalli ◽  
Marco Arreghini ◽  
Cristina Arnoldi ◽  
Benedetta Panni ◽  
Antonio Marchesoni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Juvenile Chronic Arthritis ◽  
Chronic Arthritis ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals PTEN Methylation Promotes Inflammation and Activation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Feng Li ◽  
Sha Wu ◽  
Qi Yan ◽  
Yuan-Yuan Wu ◽  
He Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Cartilage ◽  
Dna Methyltransferase ◽  
Underlying Mechanism ◽  
Cartilage Destruction ◽  
Specific Pcr ◽  
Methylation Inhibitor ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and subsequent destruction of adjacent articular cartilage and bone. In our previous work we showed that phosphatase and tension homolog deleted on chromosome 10 (PTEN) contributes to the activation of fibroblast-like synoviocytes (FLS) in adjuvant-induced arthritis (AIA), but the underlying mechanism is not unknown. In this study, we show that PTEN is downregulated while DNA methyltransferase (DNMT)1 is upregulated in FLS from RA patients and a rat model of AIA. DNA methylation of PTEN was increased by administration of tumor necrosis factor (TNF)-α in FLS of RA patients, as determined by chromatin immunoprecipitation and methylation-specific PCR. Treatment with the methylation inhibitor 5-azacytidine suppressed cytokine and chemokine release and FLS activation in vitro and alleviated paw swelling in vivo. PTEN overexpression reduced inflammation and activation of FLS via protein kinase B (AKT) signaling in RA, and intra-articular injection of PTEN-expressing adenovirus into the knee of AIA rats markedly reduced inflammation and paw swelling. Thus, PTEN methylation promotes the inflammation and activation of FLS in the pathogenesis of RA. These findings provide insight into the molecular basis of articular cartilage destruction in RA, and indicate that therapeutic strategies that prevent PTEN methylation may an effective treatment.

scholarly journals Identification of Mycoplasma fermentans in Synovial Fluid Samples from Arthritis Patients with Inflammatory Disease

2000 ◽  
Vol 38 (1) ◽  
pp. 90-93
Author(s):  
Sheena Johnson ◽  
David Sidebottom ◽  
Felix Bruckner ◽  
David Collins
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Inflammatory Cells ◽  
Juvenile Chronic Arthritis ◽  
Chronic Arthritis ◽  
Proteinase K ◽  
16S Rrna Genes ◽  
Rrna Genes ◽  
Mycoplasma Species ◽  
Mycoplasma Fermentans

ABSTRACT Since 1970 Mycoplasma fermentans has been suspected of being associated with rheumatoid arthritis. However, this association has been difficult to prove, and this has been our goal. The distribution of M. fermentans was studied in the synovial fluid of patients suffering from different arthritides. Samples of synovial fluid were taken from patients with well-defined disease and a clear diagnosis. After removal of the inflammatory cells and hyaluran, they were treated with proteinase K and tested by a single or fully nested PCR with primers directed against part of the two 16S rRNA genes of M. fermentans . The product was sequenced automatically, by using an ALF Express automatic sequencer, to confirm the mycoplasma species and to identify the strain since the two genes were usually found to be polymorphic. This was also true of the type strain, strain PG18. M. fermentans was detected in 23 of 26 (88%) rheumatoid arthritis patients, and four different strains were found. It was also found in 7 of 8 (88%) of the nonrheumatoid inflammatory arthritis patient group, which consisted of one patient with reactive arthritis, one patient with pauciarticular juvenile chronic arthritis, two patients with gout, two patients with ankylosing spondylitis, and two patients with psoriatic arthritis, only one of whom was infected with M. fermentans . It was not detected in any of the 10 osteoarthritis patients. M. fermentans was therefore found to be a variable and very common organism in arthritic patients with inflammatory joint exudates and may well prove to be important in the etiology of the diseases.

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