Naturally occurring xanthone and benzophenone derivatives exert significant anti-proliferative and proapoptotic effects in vitro on synovial fibroblasts and macrophages from rheumatoid arthritis patients

2017 ◽  
Vol 49 ◽  
pp. 148-154 ◽  
Author(s):  
Izabella Henc ◽  
Adam Kokotkiewicz ◽  
Piotr Łuczkiewicz ◽  
Ewa Bryl ◽  
Maria Łuczkiewicz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Naturally Occurring

scholarly journals Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Wei ◽  
Xiaoxun Sun ◽  
Minhui Hua ◽  
Wenfeng Tan ◽  
Fang Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
Inhibitory Effect ◽  
Antirheumatic Drug ◽  
Orphan Receptor ◽  
Rankl Expression ◽  
Articular Damage ◽  
Receptor Activator

T-614 (also named as iguratimod), a novel antirheumatic drug, could attenuate joint inflammation and articular damage in rheumatoid arthritis (RA) patients, providing a new therapy for RA. Here, we tested the role T-614 on the IL-6-induced receptor activator of nuclear factorκB ligand (RANKL)/osteoprotegerin (OPG), IL-17, and MMP-3 expression in synovial fibroblasts from rheumatoid arthritis (RASFs) patients. T-614 decreased RANKL expression and RANKL/OPG ratio in IL-6-induced RASFs. We confirmed this effect by a decrease of the mRNA and protein RANKL and mRNA RANKL/OPG in RASFs exposed in vitro to T-614 or MTX. Markedly decreased levels of IL-17, retinoid-related orphan receptor C (RORc), and MMP-3 mRNA expression were also observed in IL-6-induced RASFs in the presence of T-614 or MTX compared with those in its absence. Furthermore, T-614 blocked expression of p-ERK1/2 protein without affecting ERK1/2 expression, indicating that the way that T-614 regulated RANKL expression might be ERK1/2 pathway. Our results suggest that T-614 yields a strong improvement in arthritis via exact suppression of RANKL/OPG, IL-17, and MMP-3 expression in RASFs.

scholarly journals Loss of the WNT9a ligand aggravates the rheumatoid arthritis-like symptoms in hTNF transgenic mice

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Stefan Teufel ◽  
Petra Köckemann ◽  
Christine Fabritius ◽  
Lena I. Wolff ◽  
Jessica Bertrand ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Soft Tissue ◽  
Mouse Model ◽  
Wnt Signaling ◽  
Joint Destruction ◽  
Wnt Signaling Pathway ◽  
Synovial Fibroblasts ◽  
Canonical Wnt

AbstractAgonists and antagonists of the canonical Wnt signaling pathway are modulators of pathological aspects of rheumatoid arthritis (RA). Their activity is primarily modifying bone loss and bone formation, as shown in animal models of RA. More recently, modulation of Wnt signaling by the antagonist Sclerostin has also been shown to influence soft-tissue-associated inflammatory aspects of the disease pointing towards a role of Wnt signaling in soft-tissue inflammation as well. Yet, nothing is known experimentally about the role of Wnt ligands in RA. Here we provide evidence that altering Wnt signaling at the level of a ligand affects all aspects of the rheumatoid arthritic disease. WNT9a levels are increased in the pannus tissue of RA patients, and stimulation of synovial fibroblasts (SFB) with tumor necrosis factor (TNF) leads to increased transcription of Wnt9a. Loss of Wnt9a in a chronic TNF-dependent RA mouse model results in an aggravation of disease progression with enhanced pannus formation and joint destruction. Yet, loss of its activity in the acute K/BxN serum-transfer induced arthritis (STIA) mouse model, which is independent of TNF signaling, has no effect on disease severity or progression. Thus, suggesting a specific role for WNT9a in TNF-triggered RA. In synovial fibroblasts, WNT9a can activate the canonical Wnt/β-catenin pathway, but it can also activate P38- and downregulate NFκB signaling. Based on in vitro data, we propose that loss of Wnt9a creates a slight proinflammatory and procatabolic environment that boosts the TNF-mediated inflammatory response.

scholarly journals A Three-Dimensional Co-Culture Model for Rheumatoid Arthritis Pannus Tissue

2021 ◽  
Vol 9 ◽  
Author(s):  
Jietao Lin ◽  
Antonia RuJia Sun ◽  
Jian Li ◽  
Tianying Yuan ◽  
Wenxiang Cheng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vascular Endothelial Cells ◽  
Three Dimensional ◽  
Synovial Fibroblasts ◽  
Vascular Endothelial ◽  
3D Scaffold ◽  
Culture Model ◽  
Pannus Tissue

Three-dimensional (3D) co-culture models have closer physiological cell composition and behavior than traditional 2D culture. They exhibit pharmacological effects like in vivo responses, and therefore serve as a high-throughput drug screening model to evaluate drug efficacy and safety in vitro. In this study, we created a 3D co-culture environment to mimic pathological characteristics of rheumatoid arthritis (RA) pannus tissue. 3D scaffold was constructed by bioprinting technology with synovial fibroblasts (MH7A), vascular endothelial cells (EA.hy 926) and gelatin/alginate hydrogels. Cell viability was observed during 7-day culture and the proliferation rate of co-culture cells showed a stable increase stage. Cell-cell interactions were evaluated in the 3D printed scaffold and we found that spheroid size increased with time. TNF-α stimulated MH7A and EA.hy 926 in 3D pannus model showed higher vascular endothelial growth factor (VEGF) and angiopoietin (ANG) protein expression over time. For drug validation, methotrexate (MTX) was used to examine inhibition effects of angiogenesis in 3D pannus co-culture model. In conclusion, this 3D co-culture pannus model with biological characteristics may help the development of anti-RA drug research.

scholarly journals Optimized “In Vitro” Culture Conditions for Human Rheumatoid Arthritis Synovial Fibroblasts

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Claudia Casnici ◽  
Donatella Lattuada ◽  
Noemi Tonna ◽  
Katia Crotta ◽  
Claudio Storini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Proinflammatory Cytokines ◽  
Synovial Fibroblasts ◽  
In Vitro Studies ◽  
Tnf Alpha ◽  
Purinergic Signalling ◽  
Human Rheumatoid Arthritis ◽  
Cells Cultured

The composition of synovial fluid in rheumatoid arthritis (RA) is complex and strongly influences the microenvironment of joints and it is an inseparable element of the disease. Currently, “in vitro” studies are performed on RA cells cultured in the presence of either recombinant proinflammatory cytokines-conditioned medium or medium alone. In this study, we evaluated the use of synovial fluid, derived from RA patients, as optimal culture condition to perform “in vitro” studies on RA synovial fibroblasts. We observed that synovial fluid is more effective in inducing cell proliferation with respect to TNF-alpha or culture medium alone. Spontaneous apoptosis in fibroblasts was also decreased in response to synovial fluid. The expression of proinflammatory cytokines in the presence of synovial fluid was significantly elevated with respect to cells cultured with TNF-alpha or medium, and the overall morphology of cells was also modified. In addition, modulation of intracellular calcium dynamics elicited in response to synovial fluid or TNF-alpha exposure is different and suggests a role for the purinergic signalling in the modulation of the effects. These results emphasize the importance of using RA synovial fluid in “in vitro” studies involving RA cells, in order to reproduce faithfully the physiopathological environmental characteristic of RA joints.

Sign in / Sign up

Export Citation Format

Share Document