scholarly journals Synovial lining cell hyperplasia in rheumatoid arthritis: dogma and fact.

1988 ◽  
Vol 47 (4) ◽  
pp. 348-349 ◽  
Author(s):  
B Henderson ◽  
P A Revell ◽  
J C Edwards
1987 ◽  
Vol 80 (8) ◽  
pp. 477-478
Author(s):  
D W Howat

A perplexing feature of rheumatoid arthritis is the increase in the number of synovial lining cells with no mitotic activity. This feature has been investigated in the rabbit model. Rabbits with the established condition were injected into the affected joint with tritiated thymidine and killed either up to 24 hours later, or at 3 or 7 days. The location of labelled cells, detected by autoradiography, showed the label predominantly in the stroma in the former, and mainly in the lining cells in the latter, indicating that the lining cells were derived by recruitment from active cells deep in the stroma.


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 ◽  
...  

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 726-733 ◽  
Author(s):  
EM Conway ◽  
B Nowakowski

Abstract Thrombomodulin (TM) is a transmembrane glycoprotein that interacts with thrombin, thereby serving as a cofactor in the activation of protein C, a major physiologically relevant natural anticoagulant. Although initially described as a vascular endothelial cell receptor, TM has also been reported to be synthesized by several cells, including megakaryocytes, platelets, monocytes, neutrophils (PMN), mesothelial cells, and synovial lining cells. A prominent feature of rheumatoid arthritis (RA) is infiltration of PMN into the joint space. To determine whether TM might play a role in the inflammatory process, we examined synovial fluid for the presence of TM in 10 patients with RA and five patients with osteoarthritis (OA). We determined that the mean synovial fluid and plasma TM levels in the OA group were 23.5 ng/mL and 24.2 ng/mL, respectively, whereas those with RA had a significantly elevated mean synovial fluid TM level of 136.2 ng/mL as compared with the plasma TM concentration of 43.9 ng/mL (P < .05). Synovial fluid TM levels did not correlate with PMN counts (r = .261). Purified TM from synovial fluid was identical in molecular weight to plasma-derived TM and was biologically functional with respect to protein C cofactor activity. Using direct immunofluorescence, we determined that adherent cultured synovial fluid cells that are not monocytoid in origin express surface and cytoplasmic TM, thereby providing an alternative source of the protein. Biologic activity of the cell-surface TM was confirmed by acceleration of thrombin-dependent protein C activation. Northern analysis of RNA extracted from the cultured cells indicated that TM messenger RNA was present, suggesting local synthesis. Our results indicate that in RA-associated synovial effusions, biologically active TM is increased, the source of which may be from plasma, PMN, and/or synovial lining cells. TM may play a regulatory role either in fibrin deposition in the inflamed joint and/or in the progression of the inflammatory process.


1991 ◽  
Vol 231 (2) ◽  
pp. 145-155 ◽  
Author(s):  
William D. Meek ◽  
Brian T. Raber ◽  
Oza M. McClain ◽  
Jeff K. McCosh ◽  
B. B. Baker

2018 ◽  
Vol 77 (11) ◽  
pp. 1636-1643 ◽  
Author(s):  
Marta F Bustamante ◽  
Patricia G Oliveira ◽  
Ricard Garcia-Carbonell ◽  
Adam P Croft ◽  
Jeff M Smith ◽  
...  

ObjectivesRecent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage.MethodsHK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2F/F mice harbouring Col1a1-Cre (HK2Col1), to delete HK2 in non-haematopoietic cells.ResultsHK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage.ConclusionHK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.


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