Correction to: Destructive Roles of Fibroblast-Like Synoviocytes in Chronic Inflammation and Joint Damage in Rheumatoid Arthritis

Erosive destruction of joint structures is a critical event in the progression of rheumatoid arthritis (RA), in which fibroblast-like synoviocytes (FLS) are the primary effectors. We previously reported that the ability of RA FLS to degrade extracellular matrix (ECM) components depends on the formation of actin-rich membrane protrusions, called invadosomes, through processes that remain elusive. 14-3-3η belongs to a family of scaffolding proteins involved in a wide range of cellular functions, and its expression is closely related to joint damage and disease activity in RA patients. In this study, we sought to assess the role of 14-3-3η in joint damage by examining its contribution to the invadosome formation phenotype of FLS. Using human primary FLS, we show that 14-3-3η expression is closely associated with their ability to form invadosomes. Furthermore, knockdown of 14-3-3η using shRNAs decreases the level of invadosome formation in RA FLS, whereas addition of the recombinant protein to FLS from healthy individuals promotes their formation. Mechanistic studies suggest that 14-3-3η regulates invadosome formation by increasing Snail expression, a mechanism that involves nuclear exclusion of the transcription repressor FOXO3. Our results implicate the 14-3-3η–FOXO3–Snail axis in promoting the aggressive ECM-degrading phenotype of RA FLS, and suggest a role for this scaffolding protein in cartilage degradation.

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Anti-Inflammatory Effects of TRAF-Interacting Protein in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Mediators of Inflammation ◽

10.1155/2016/3906108 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Qing-Zhu Kong ◽

Li-Tao Guo ◽

Jia-Ning Yang ◽

Yan-Fei Wang ◽

Jing-Xin Zhao ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Proinflammatory Cytokines ◽

Transforming Growth Factor ◽

Proteolytic Enzymes ◽

Joint Damage ◽

Cartilage Destruction ◽

Interacting Protein ◽

Systemic Inflammatory Disease ◽

Anti Inflammatory ◽

Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS. Overexpression of TRIP significantly inhibited the activation of NF-κB signaling and decreased the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) in TNFα-stimulated RA-FLS. Furthermore, TRIP was found to interact with transforming growth factorβ-activated kinase 1 (TAK1) and promoting K48-linked polyubiquitination of TAK1 in RA-FLS. Our results demonstrate that TRIP has anti-inflammatory effects on RA-FLS and suggest TRIP as a potential therapeutic target for human RA.

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Hand bone loss measured by digital X-ray radiogrammetry is a predictor of joint damage in early rheumatoid arthritis

Scandinavian Journal of Rheumatology ◽

10.1080/03009740902939376 ◽

2009 ◽

pp. 1-8

Author(s):

K. Forslind ◽

A. Boonen ◽

K. Albertsson ◽

I. Hafstrom ◽

B. Svensson ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Loss ◽

Early Rheumatoid Arthritis ◽

Joint Damage ◽

X Ray

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HYPERBARIC OXYGENATION IN COMPLEX THERAPY OF RHEUMATOID ARTHRITIS IN PATIENTS WITH CONCOMITANT ANEMIA

Ulyanovsk Medico-biological Journal ◽

10.34014/2227-1848-2020-1-42-52 ◽

2020 ◽

pp. 42-52

Author(s):

T.S. Golubtsova ◽

A.B. Peskov ◽

S.V. Peskova ◽

M.P. Markevich ◽

V.V. Gnoevykh ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Chronic Inflammation ◽

Hyperbaric Oxygenation ◽

Joint Inflammation ◽

Primary Objective ◽

Hemoglobin Level ◽

Standard Scheme ◽

Comparison Results ◽

Complex Therapy ◽

Activity Indices

Anemia occurs in approximately 30–70 % of patients with rheumatoid arthritis (RA). The most common cause of low hemoglobin level is chronic inflammation. Hyperbaric oxygenation (HBO) reduces the chronic inflammatory process, hypoxia severity and stimulates erythropoiesis. Therefore, HBO can be considered as one of the promising methods for treating anemia of chronic inflammation. The primary objective of the study is to carry out the efficacy analysis of rheumatoid arthritis (RA) complex therapy using hyperbaric oxygenation (HBO) for comparison results in patients with anemia and with a normal hemoglobin level. Materials and Methods. To assess the advisability of HBO in patients with RA and concomitant anemia, we analyzed indicators of RA activity and local joint inflammation in 120 patients. 30 patients were treated according to the standard scheme, 30 patients underwent one and 60 patients – five additional HBO sessions (1.3 atm during 40 min). Patients who underwent HBO were divided into two subgroups with normal and low hemoglobin levels. Results. On the 14th day of inpatient hospitalization, we fixed decrease in RA activity indices in all groups. The decrease in the activity of RA and local joint inflammation in patients who underwent HBO was faster than in patients who were treated according to the standard scheme, and in patients who underwent only one HBO session. Better results were observed in patients with concomitant anemia compared with patients with normal hemoglobin level. It was confirmed by a significant decrease in acute-phase blood values (ESR and CRP) and RA activity indices (assessment of disease activity (by a doctor and by a patient), CDIA, SDIA and DAS28). Conclusion. Additional HBO in complex RA therapy contributes to the efficacy of inpatient treatment. The most pronounced effect is observed in patients with both RA and anemia. Keywords: hyperbaric oxygenation, rheumatoid arthritis, anemia. Анемия встречается у 30–70 % больных, страдающих ревматоидным артритом (РА). Наиболее частой причиной снижения уровня гемоглобина крови является хроническое воспаление. Гипербарическая оксигенация (ГБО) способствует уменьшению активности хронического воспалительного процесса, выраженности гипоксии и стимулирует эритропоэз, следовательно, применение ГБО можно рассматривать как один из перспективных методов лечения анемии хронического воспаления. Цель работы – провести сравнительный анализ эффективности комплексной терапии пациентов, страдающих ревматоидным артритом, с включением курса гипербарической оксигенации на фоне анемии и при нормальном значении уровня гемоглобина крови. Материалы и методы. Для оценки целесообразности проведения курса ГБО у больных, страдающих РА с сопутствующей анемией, проведен динамический анализ показателей активности РА и локального воспаления в суставе у 120 пациентов (30 пациентов получили лечение по стандартной схеме, 30 больных дополнительно прошли 1 сеанс ГБО и 60 пациентов прошли 5 сеансов ГБО при 1,3 атм в течение 40 мин). Пациенты, прошедшие курс ГБО, были разделены на две подгруппы: с нормальным и сниженным уровнем гемоглобина. Результаты. На 14-й день госпитализации у всех пациентов отмечали регресс клинических проявлений артрита. Снижение показателей активности РА и локального воспаления в суставе у пациентов, прошедших курс ГБО, происходило быстрее, чем у больных, получивших лечение по стандартной схеме, и пациентов, прошедших один сеанс ГБО. Более высокие результаты лечения получены у больных с сопутствующей анемией по сравнению с пациентами с нормальными значениями гемоглобина, что подтверждено значимым снижением острофазовых показателей крови (СОЭ и СРБ) и индексов активности РА (ООАВ, ООАБ, CDIA, SDIA и DAS28). Выводы. Включение курса ГБО в стандартную схему терапии РА повышает эффективность стационарного лечения. Наиболее выраженный эффект наблюдается у больных с РА и анемией. Ключевые слова: гипербарическая оксигенация, ревматоидный артрит, анемия.

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Faculty Opinions recommendation of Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108991.565450 ◽

2008 ◽

Author(s):

Martin Aringer ◽

Alexander Kleymann

Keyword(s):

Rheumatoid Arthritis ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Joint Damage ◽

Tumour Necrosis Factor Inhibitor ◽

Inadequate Response ◽

Structural Joint ◽

Factor Inhibitor ◽

Necrosis Factor

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Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666191210110826 ◽

2020 ◽

Vol 21 (8) ◽

pp. 734-740 ◽

Cited By ~ 1

Author(s):

Shou-di He ◽

Ning Tan ◽

Chen-xia Sun ◽

Kang-han Liao ◽

Hui-jun Zhu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Caspase 3 ◽

Joint Destruction ◽

Joint Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Caspase 9 ◽

Inflammatory Processes ◽

Related Proteins ◽

Local Stimulation ◽

Fibroblast Like Synoviocytes

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.

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Anti-carbamylated Protein Antibodies and Serum Level of 14-3-3 Protein for Early Detection of Rheumatoid Arthritis Patient in Correlation with Rheumatoid Factor, Anti-CCP Antibodies, Disease Activity and Joint Damage using High Frequency Musculoskeletal Ultrasound

Applied Clinical Research Clinical Trials and Regulatory Affairs ◽

10.2174/2213476x07666200120111549 ◽

2020 ◽

Vol 7 (2) ◽

pp. 141-153

Author(s):

Sahar A. Ahmed ◽

Enas M. Darwish ◽

Walaa A. Attya ◽

Mai Samir ◽

Mennatallah Elsayed ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Rheumatoid Factor ◽

Disease Activity Score ◽

Joint Damage ◽

Musculoskeletal Ultrasound ◽

Activity Score ◽

Das 28 ◽

Significant Difference ◽

Hands And Feet

Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and disability. Although progress has been made in exploring RA nature, still there is a lot to know about the disease pathogenesis, diagnosis, and treatment. Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency musculoskeletal ultrasound used to assess the disease activity and joint damage. Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness IMT) were used in assessing the RA disease. Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1- 8.9 U⁄ml) compared to the control 3.2(1.9- 4.3 U⁄ml) (p< 0.001) but 14-3-3η showed no significant difference. There was a significant positive correlation between anti-carbamylated protein antibodies, 14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound. There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14- 3-3η had 51.9% sensitivity and 72.1% specificity. Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity in RA diagnosis and had a correlation with the disease activity and joint damage.

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