Induction of collagenase synthesis in chondrocytes by a factor synthesized by inflamed synovial tissue

1994 ◽  
Vol 43 (3-4) ◽  
pp. 206-210
Author(s):  
S. S. Kerwar ◽  
Susan C. Ridge ◽  
M. Jane Landes ◽  
Joseph C. Nolan ◽  
Arnold L. Oronsky
Keyword(s):  
Synovial Tissue

Mitochondria microcrystals deposition in some inherited diseases of lipid metabolism.

1978 ◽  
Vol 36 (2) ◽  
pp. 256-257
Author(s):  
S. Laoussadi ◽  
A. Kahan ◽  
G. Aubouy ◽  
F. Delbarre
Keyword(s):  
Synovial Tissue ◽  
Storage Disease ◽  
Metabolic Diseases ◽  
Uranyl Acetate ◽  
List Type ◽  
Type Ii ◽  
Type Number ◽  
Lipid Storage Disease ◽  
Thin Sections ◽  
Mean Size

Several patients with Fabry's, Gaucher's diseases and hyperlipoproteinemia type II and with arthropatic manifestations were observed.As no histological explanation for these symptoms was available,an ultrastructural study of synovial tissue was done to establish an anatomoclinical relation.Material and Methods :synovial membrane samples were obtained by needle biopsies of the knee from three patients with arthropatic manifestations of each disease.They were fixed in 5% glutaraldehyde, postfixed in 1% osmium tetraoxyde and embedded in Epon 812. Thin sections coloured by uranyl acetate and lead citrate were observed with an Elmiskop I Siemens electron microscope.Two important phenomena were observed in synovial tissue:Specific patterns of each lipid storage disease,which are now well known.In all the three metabolic diseases, hydroxyapatite-like crystals were found. They are characterized by their intramitochondrial localization, without any relation with cristae,an anarchic disposition and a mean size of 550 A.Crystals may be found also free in the cytoplasm of synoviocytes Some micrographs suggest an evolution in four steps :a. mitochondria with only a few microcrystalsb. mitochondria stuffed with these structuresc. disruption of mitochondria membranesd. microcrystals appear free in the cytoplasm

Appearance of Anti-HLA-DR-Reactive Cells in Normal and Rheumatoid Synovial Tissue

1981 ◽  
Vol 14 (2) ◽  
pp. 183-192 ◽  
Author(s):  
L. KLARESKOG ◽  
U. FORSUM ◽  
U. MALMNAS TJERNLUND ◽  
D. KABELITZ ◽  
A. WIGREN
Keyword(s):  
Synovial Tissue ◽  
Hla Dr ◽  
Rheumatoid Synovial Tissue

scholarly journals Highly enhanced expression of the disintegrin metalloproteinase MDC15 (metargidin) in rheumatoid synovial tissue

2001 ◽  
Vol 44 (9) ◽  
pp. 2046-2054 ◽  
Author(s):  
Beate B. B�hm ◽  
Thomas Aigner ◽  
Carl P. Blobel ◽  
Joachim R. Kalden ◽  
Harald Burkhardt
Keyword(s):  
Synovial Tissue ◽  
Rheumatoid Synovial Tissue ◽  
Enhanced Expression

scholarly journals Synovial Tissue Proteins and Patient-Specific Variables as Predictive Factors for Temporomandibular Joint Surgery

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 46
Author(s):  
Mattias Ulmner ◽  
Rachael Sugars ◽  
Aron Naimi-Akbar ◽  
Nikolce Tudzarovski ◽  
Carina Kruger-Weiner ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Synovial Tissue ◽  
Surgical Outcome ◽  
Clinical Decision Making ◽  
Protein Profile ◽  
Strong Association ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Patient Specific ◽  
Disc Displacement ◽  
Patient Reported

Our knowledge of synovial tissues in patients that are scheduled for surgery as a result of temporomandibular joint (TMJ) disorders is limited. Characterising the protein profile, as well as mapping clinical preoperative variables, might increase our understanding of pathogenesis and forecast surgical outcome. A cohort of 100 patients with either disc displacement, osteoarthritis, or chronic inflammatory arthritis (CIA) was prospectively investigated for a set of preoperative clinical variables. During surgery, a synovial tissue biopsy was sampled and analysed via multi-analytic profiling. The surgical outcome was classified according to a predefined set of outcome criteria six months postoperatively. Higher concentrations of interleukin 8 (p = 0.049), matrix metalloproteinase 7 (p = 0.038), lumican (p = 0.037), and tissue inhibitor of metalloproteinase 2 (p = 0.015) were significantly related to an inferior surgical outcome. Several other proteins, which were not described earlier in the TMJ synovia, were detected but not related to surgical outcome. Bilateral masticatory muscle palpation pain had strong association to a poor outcome that was related to the diagnoses disc displacement and osteoarthritis. CIA and the patient-reported variable TMJ disability might be related to an unfavourable outcome according to the multivariate model. These findings of surgical predictors show potential in aiding clinical decision-making and they might enhance the understanding of aetiopathogenesis in TMJ disorders.

scholarly journals POS0387 ACPA STATUS CORRELATES WITH DIFFERENTIAL IMMUNE PROFILE OF RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 423.2-424
Author(s):  
A. Floudas ◽  
M. Canavan ◽  
T. McGarry ◽  
V. Krishna ◽  
S. Nagpal ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Synovial Tissue ◽  
Peripheral Blood ◽  
Flow Cytometric Analysis ◽  
Algorithm Analysis ◽  
Treat To Target ◽  
Tnf Α ◽  
Acpa Status

Background:Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20-30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology. Elucidating the underlying mechanisms of disease pathogenesis could inform a treat to target approach for both ACPA-positive and ACPA-negative RA patients.Objectives:To identify peripheral blood and synovial tissue immune population differences that associate with RA disease endotype.To identify unique RA patient synovial tissue gene signatures and enriched pathways that correlate with ACPA status.Methods:Detailed high dimensionality flow cytometric analysis with supervised and unsupervised algorithm analysis of ACPApos and ACPAneg RA patient peripheral blood and synovial tissue single cell suspensions. Ex vivo peripheral blood and synovial tissue T cell stimulation and cytokine production characterisation. RNAseq analysis with specific pathway enrichment analysis of APCApos and ACPAneg RA patient synovial tissue biopsies.Results:Detailed profiling based on high dimensionality flow cytometric analysis of key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells, T peripheral helper cells (Tph) and CD4 T cell proinflammatory cytokine responses with supervised and unsupervised algorithm analysis revealed unique RA patient peripheral blood B cell and Tfh cell profiles. ACPApos RA patients were characterised by significantly (*P=0.03) increased frequency of Tfh (CXCR5+CD4+) cells and distinct clustering influenced by increased switched (IgD-CD27+) and DN (IgD-CD27-) memory B cells compared to APCAneg RA patients. Surprisingly synovial tissue B cell subpopulation distribution was similar between ACPAneg and ACPApos RA patients, with significant accumulation of switched and double negative memory B cells, highlighting a key role for specific B cell subsets in both disease endotypes. Interestingly, synovial tissue CD4 T cell proinflammatory cytokine (TNF-α, IFN-γ, IL-2, GM-CSF, IL-17A, IL-22, IL-4) production was markedly different between ACPAneg and APCApos RA patients with hierarchical clustering and PCA analysis revealing endotype specific cytokine profiles with ACPAneg RA patient synovial T cells showing increased TNF-α (P=0.01) expression. RNAseq analysis of RA patient synovial tissue revealed significant disease endotype specific gene signatures with specific enrichment for B cell receptor signalling and T cell specific pathways in ACPApos compared to ACPAneg RA patients. Additionally, significantly different chemokine receptor expression based on RA patient ACPA status was observed with increased CXCR3 (P<0.001), CCR7 (P=0.002), and CCR2 (P=0.004) but decreased CXCR7 (P=0.007) expression in APCApos compared to ACPAneg RA patient synovial biopsies.Conclusion:ACPA status associates with unique synovial tissue immune cell and gene profile signatures highlighting differences in the underlying immunological mechanisms involved, therefore reinforcing the need for a treat to target approach for both endotypes of RA.Figure 1.RNAseq analysis of synovial tissue biopsies revealed specific T cell related pathway enrichment in ACPA positive compared to ACPA negative RA patients (n=50, analysis performed with the DESq2 and pathfindeR pipelines in R).Disclosure of Interests:Achilleas Floudas: None declared, Mary Canavan: None declared, Trudy McGarry Employee of: Novartis, Vinod Krishna Employee of: Janssen, Sunil Nagpal Employee of: Janssen, GSK, Douglas Veale Speakers bureau: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Consultant of: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Grant/research support from: Janssen, Abbvie, Pfizer, UCB, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Janssen, Abbvie, Pfizer, UCB

scholarly journals Mechanism of miR-218-5p in autophagy, apoptosis and oxidative stress in rheumatoid arthritis synovial fibroblasts is mediated by KLF9 and JAK/STAT3 pathways

2021 ◽  
pp. jim-2020-001437
Author(s):  
Ming Chen ◽  
Minghui Li ◽  
Na Zhang ◽  
Wenwen Sun ◽  
Hui Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Signaling Pathway ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Reverse Transcription Pcr ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Interfering Rna ◽  
And Oxidative Stress

This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription–PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3′ untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.

scholarly journals THU0070 DEFINING SYNOVIAL SIGNATURES IN THE RAT CIA MODEL: WHAT CAN WE LEARN ABOUT RA PROGRESSION?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 247.2-248
Author(s):  
D. Ruelas ◽  
R. LI ◽  
C. Franci ◽  
V. Lira ◽  
D. Lopez ◽  
...  
Keyword(s):  
Disease Progression ◽  
Synovial Tissue ◽  
Current Knowledge ◽  
Severe Disease ◽  
Unmet Need ◽  
Poor Response ◽  
Multiple Time ◽  
Combination Therapies ◽  
Course Of Disease ◽  
Time Point

Background:Patients showing inadequate or no response to current therapies represent a key unmet need in rheumatoid arthritis (RA). To address this, novel or combination therapies are of high clinical interest. Identification of novel therapeutic targets requires a greater understanding of the pathogenic molecular drivers in the RA synovium. However, our current knowledge of human molecular patterns that emerge as a result of disease progression is complicated by patient-to-patient heterogeneity and access to synovial tissue.Objectives:Here we use the current knowledge of human synovial heterogeneity to conduct a longitudinal study of global molecular responses in the rat collagen-induced arthritis (CIA) model to better understand synovial biology, improve the preclinical modeling of human disease, and discover novel targets for RA.Methods:A rat CIA model was performed as previously described.1RNA-Seq was performed on 56 knee synovial tissues collected at multiple time points throughout the course of disease. Differential gene expression was determined at each individual time point and longitudinally with disease progression. Published human synovial datasets were used to categorize these genes into myeloid, lymphoid, fibroid, and low inflammatory signatures.2Differentially expressed genes (DEGs) at each time point were compared to human synovial datasets of RA patients before and after treatment. In addition, we compared disease-driven genes in CIA to genes in RA patients that are unchanged following therapy to identify possible combination therapies.Results:Disease pathology in the rat CIA natural history study progressed as expected: significant decreases were seen in body weight, as well as increases in ankle diameter, paw weight, and histopathology scores of joints in collagen-injected vs noninjected rats. There were 1900 DEGs identified between diseased and naïve rats over the course of disease, representing disease-induced gene signatures (Fig. 1). Comparing these DEGs to reported human RA synovial signatures, both the lymphoid and myeloid signatures were found to be highly upregulated. Interestingly, there were no significant DEGs representing the human fibroid and low inflammatory synovial signatures identified in the CIA rat model. This suggests that the rat CIA model most closely models RA patients with an immune synovial phenotype. In addition, we examined the overlap between disease-driven genes in CIA and genes in RA patients that are unchanged following therapy to identify signaling pathways that may be of utility in combination therapy. Of genes that were upregulated in CIA, 94% of genes that mapped to extracellular matrix-receptor pathways remained unchanged in the synovial tissue of RA patients following tocilizumab treatment.Conclusion:Previous studies have shown that nearly 30% of treatment-naïve early RA patients exhibit a strong fibroid phenotype that correlates with less severe disease and a relatively poor response to disease-modifying anti-rheumatic drugs.3These data indicate that the synovial biology associated with such patients (fibroid or pauci-immune) is not well captured in CIA, the most common preclinical RA model. To assess potential new therapies targeting these patients, it will be necessary to develop alternative animal models with more intact fibroid signatures. In addition to these findings, we also characterized the global molecular changes that occur with disease progression in the CIA rat and made a comparison to RA patients on treatment, providing an overall understanding of disease-relevant pathways in the synovium that may point to possible combination therapies.References:[1]Trentham DE, et al.J Exp Med. 1977;146(3):857-868.[2]Dennis G Jr, et al.Arthritis Res Ther. 2014;16(2):R90.[3]Humby F, et al.Ann Rheum Dis. 2019;78(6):761-772.Disclosure of Interests:Debbie Ruelas Employee of: Gilead, Ruidong Li Employee of: Gilead, Christian Franci Employee of: Gilead, Victor Lira Employee of: Gilead, David Lopez Employee of: Gilead, Li Li Employee of: Gilead, Gundula Min-Oo Employee of: Gilead, Julie A. Di Paolo Employee of: Gilead

Synovial immunopathology in haemochromatosis arthropathy

2009 ◽  
Vol 69 (6) ◽  
pp. 1214-1219 ◽  
Author(s):  
Gisela Ruiz Heiland ◽  
Elmar Aigner ◽  
Tomáš Dallos ◽  
Enijad Sahinbegovic ◽  
Veit Krenn ◽  
...  
Keyword(s):  
Synovial Tissue ◽  
Autosomal Recessive ◽  
Mononuclear Cells ◽  
Cartilage Degradation ◽  
Grading System ◽  
Synovial Hyperplasia ◽  
Hereditary Haemochromatosis ◽  
Low Degree ◽  
Articular Damage ◽  
Musculoskeletal Involvement

BackgroundHereditary haemochromatosis (HH) is a common autosomal recessive inherited disorder that frequently causes arthritis. The pathophysiology of musculoskeletal involvement is, however, unclear.ObjectiveTo analyse synovial tissue obtained at surgery from patients with HH arthropathy and compare it qualitatively and quantitatively with specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).MethodsSynovial tissue from 15 patients with HH, 20 with RA and 39 with OA was obtained during surgery. A synovitis grading system was used to determine the severity of synovial inflammation. Using immunohistochemistry, synovial neovascularisation and infiltration of macrophages, neutrophils and lymphocytes were quantitatively assessed.ResultsSynovitis in HH arthropathy largely resembles OA with mild infiltration of mononuclear cells and lymphocytes, formation of synovial microvessels and a low degree of synovial hyperplasia. While many features of HH arthropathy are reminiscent of OA, macrophage and especially neutrophil invasion is clearly more prominent in HH arthropathy than in primary OA and mimics features of RA. This finding was observed particularly in synovial tissue of HH samples with marked haemosiderin deposition.DiscussionThe histological picture of the synovium in HH arthropathy largely resembles a process reminiscent of OA. Neutrophil invasion is, however, markedly increased in HH arthropathy, especially in joints with iron deposition. Accumulation of neutrophils may be crucial for the production of matrix enzymes, which enables cartilage degradation and more rapidly progressive articular damage.

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