scholarly journals The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes of the hyperplastic synovial lining layer in rheumatoid arthritis

2011 ◽  
Vol 13 (2) ◽  
Author(s):  
Anna-Karin H Ekwall ◽  
Thomas Eisler ◽  
Christian Anderberg ◽  
Chunsheng Jin ◽  
Niclas Karlsson ◽  
...  
2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 934.3-934
Author(s):  
M. Kim ◽  
Y. Choe ◽  
H. Lee ◽  
Y. H. Cheon ◽  
S. I. Lee

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 422.2-423
Author(s):  
B. van Dijk ◽  
F. Wouters ◽  
E. van Mulligen ◽  
M. Reijnierse ◽  
A. van der Helm - van Mil

Background:Inflammation of the synovial lining is a hallmark of rheumatoid arthritis (RA). A synovial lining is not only present at synovial joints and tendon sheaths but also at bursae. Inflammation of the synovium-lined intermetatarsal bursae in the forefoot, intermetatarsal bursitis (IMB), was recently identified with MRI. It is specific for early RA and present in the majority of RA patients at diagnosis. During development of RA, MRI-detectable subclinical synovitis and tenosynovitis often occur before clinical arthritis presents. Whether IMB is also present in a pre-arthritis stage is unknown.Objectives:To assess the occurrence of IMB in patients with clinically suspect arthralgia (CSA) and its association with progression to clinical arthritis in a large MRI-study.Methods:We studied 524 consecutive patients presenting with CSA. CSA was defined as recent-onset arthralgia of small joints that is likely to progress to RA based on the clinical expertise of the rheumatologist. Participants underwent unilateral contrast-enhanced 1.5T MRI of the forefoot, metacarpophalangeal (MCP) joints and wrist at baseline. Thereafter patients were followed for detection of clinical arthritis, as identified at physical joint examination by the rheumatologist. Baseline MRIs were evaluated for IMB at all 4 intermetatarsal spaces. Also synovitis, tenosynovitis and osteitis were assessed in line with the RA MRI scoring system (summed as RAMRIS-inflammation). Both IMB and RAMRIS-inflammation were dichotomised into positive/negative using data from age-matched symptom-free controls as a reference. Cox regression analysed the association of IMB with progression to clinical arthritis; multivariable analyses were used to adjust for RAMRIS-inflammation which is known to associate with progression to clinical arthritis. Analyses were repeated stratified for ACPA-status, since ACPA-positive and ACPA-negative RA are considered separate entities with differences in pathophysiology.Results:The baseline MRIs showed ≥1 IMB in 35% of CSA-patients. Patients with IMB were more likely to also have synovitis (OR 2.5 (95%CI 1.2–4.9)) and tenosynovitis (8.9 (3.4–22.9)) on forefoot MRI, but not osteitis (0.9 (0.5–1.8)). Patients were followed for median 25 months (IQR 19–27). IMB-positive patients developed clinical arthritis more often than IMB-negative patients (HR 3.0 (1.9-4.8)). This association was independent of RAMRIS-inflammation (adjusted HR 2.2 (1.4–3.6)). In stratified analyses, IMB was more frequent in ACPA-positive than in ACPA-negative CSA (68% vs. 30%, p<0.001). Moreover IMB predicted clinical arthritis development in ACPA-positive CSA (HR 2.5 (1.1–5.7)) but not in ACPA-negative CSA patients (1.0 (0.5–2.2)).Conclusion:One-third of CSA patients have IMB. IMB is frequently present in conjunction with subclinical synovitis and tenosynovitis. It precedes the development of clinical arthritis, and in particular the development of ACPA-positive RA. These results reinforce the notion that not only intra- but also juxta-articular synovial inflammation is involved in the development of RA.Disclosure of Interests:None declared


2013 ◽  
Vol 72 (Suppl 1) ◽  
pp. A5.2-A5
Author(s):  
ON Karpus ◽  
B Niederreiter ◽  
PP Tak ◽  
JS Smolen ◽  
HP Kiener ◽  
...  

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