scholarly journals Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis

2019 ◽  
Vol 20 (22) ◽  
pp. 5552 ◽  
Author(s):  
Daniela Cici ◽  
Addolorata Corrado ◽  
Cinzia Rotondo ◽  
Francesco P. Cantatore
Keyword(s):  
Rheumatoid Arthritis ◽  
Wnt Signaling ◽  
Cellular Proliferation ◽  
Biological Therapy ◽  
Wnt Signaling Pathway ◽  
Tnf Α ◽  
Bone Complications ◽  
Necrosis Factor

The Wnt signaling pathway plays a key role in several biological processes, such as cellular proliferation and tissue regeneration, and its dysregulation is involved in the pathogenesis of many autoimmune diseases. Several evidences support its role especially in bone complications of rheumatic diseases. In Rheumatoid Arthritis (RA), the Wnt signaling is implicated in systemic and localized bone loss, while available data of its role in Spondyloarthritis (SpA) are conflicting. In the last few decades, the quality of life of rheumatic patients has been dramatically improved by biological therapy, targeting cytokines involved in the pathogenesis of these diseases like tumor necrosis factor (TNF)α, interleukin (IL)-1, IL-6, IL-17. In this review, we reviewed the role of Wnt signaling in RA and SpA, focusing on the effect of biological therapy on this pathway and its possible clinical implications.

Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti–tumor necrosis factor-α antibody therapy

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 474-482 ◽  
Author(s):  
Helen A. Papadaki ◽  
Heraklis D. Kritikos ◽  
Vasilis Valatas ◽  
Dimitrios T. Boumpas ◽  
George D. Eliopoulos
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Chronic Disease ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Anemia Of Chronic Disease ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Circumstantial evidence has implicated tumor necrosis factor α (TNF-α) in the pathogenesis of anemia of chronic disease (ACD) in rheumatoid arthritis (RA). We investigated the role of TNF-α in erythropoiesis of patients with active RA (n = 40) and the effect of anti–TNF-α antibody administration (cA2). Patients with RA had lower numbers of CD34+/CD71+ and CD36−/glycophorin A+ (glycoA+) bone marrow (BM) cells and increased proportions of apoptotic cells within the CD34+/CD71+ and CD36+/glycoA+ cell compartments, compared to healthy controls (n = 24). Erythroid burst-forming units (BFU-Es) obtained by BM mononuclear or purified CD34+ cells were significantly lower in RA patients compared to controls. These abnormalities were more pronounced among patients with ACD. Increased TNF-α levels in patient long-term BM culture supernatants inversely correlated with BFU-Es and hemoglobin levels and positively with the percentage of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells. Following cA2 therapy, a normalization was documented in the number of CD34+/CD71+ and CD36−/glycoA+ cells, the number of BFU-Es, and the proportion of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells, which was associated with a significant increase in hemoglobin levels compared to baseline. Recovery from anemia was more prominent in patients with ACD. The exogenous addition of an anti–TNF-α antibody in the cultures increased BFU-E number in patients prior to cA2 treatment but not after treatment, further substantiating the inhibitory role of TNF-α on patients' erythropoiesis. We conclude that TNF-α–mediated apoptotic depletion of BM erythroid cells may account for ACD in RA and that cA2 administration may ameliorate ACD in these patients by down-regulating the apoptotic mechanisms involved in erythropoiesis.

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 Association of Estrogen Receptor 1 and Tumor Necrosis Factor α Polymorphisms with Temporomandibular Joint Anterior Disc Displacement without Reduction

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bartosz Dalewski ◽  
Agata Kamińska ◽  
Katarzyna Białkowska ◽  
Anna Jakubowska ◽  
Ewa Sobolewska
Keyword(s):  
Temporomandibular Joint ◽  
Temporomandibular Joint Disorders ◽  
Control Group ◽  
Disc Displacement ◽  
Anterior Disc Displacement ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objectives. The aim of this study was to investigate the role of ESR1 rs1643821 and TNF-α rs1800629 as potential genetic factors regulating anterior disc displacement without reduction-mediated inflammatory pathway. Background. The temporomandibular joint is a complex synovial joint that allows mandibular movement in three directions. Although temporomandibular disorders are widespread, limited data is available on the biochemical characteristics of the displaced disc and quality of the surrounding soft tissue. Changes in degenerative tissue provoke disc displacement which involves secretion of inflammatory markers and sequential conversion of fibroblast-like cells into chondrocyte-like cells. Due to the high occurrence in female adolescents, the potential role of sex hormones in temporomandibular joint disorders has been speculated. Furthermore, anterior disc displacement without reduction severely affects the quality of life. Methods. 124 Caucasian patients with a history of at least one anterior disc displacement without reduction within 3 months were enrolled. Anterior disc displacement without reduction was diagnosed based on clinical examination, diagnostic criteria (DC)/TMD, and cone-beam computed tomography/magnetic resonance imaging (CBCT/MRI). The control group consisted of 126 patients with no temporomandibular joint disorders. Genotyping of two single nucleotide polymorphisms, estrogen receptor 1 (ESR1) rs1643821, and tumor necrosis factor α (TNF-α) rs1800629 was performed. Results. ESR1 rs1643821 showed significant P values (using chi-square analysis) revealing the difference in anterior disc displacement without reduction frequencies while TNF-α rs1800629 polymorphism was found to be statistically insignificant when compared to the control group. Furthermore, patients with a genotype of ESR1 rs1643821 showed a decreased probability ( OR = 0.412 ) against anterior disc displacement without reduction when compared to the GG genotype ( OR = 1 ). Conclusion. ESR1 rs1643821 with A allele frequency was lower in patients with anterior disc displacement without reduction compared to the control group. Thus, the rs1643821 variant is significantly associated with susceptibility to the anterior disc displacement without a reduction in European Caucasians. Conversely, TNF-α rs1800629 was a statistically insignificant factor against anterior disc displacement without reduction when compared to the control group.

Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Platelet Rich Plasma ◽  
Joint Inflammation ◽  
Monthly Interval ◽  
Post Injection ◽  
Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

THE EVALUATION OF SERUM SEROTONIN LEVEL AMONG PATIENTS WITH CROHN’S DISEASE AND ITS IMPACT ON QUALITY OF LIFE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S55-S55
Author(s):  
Marcin Sochal ◽  
Piotr Bialasiewicz ◽  
Agata Gabryelska ◽  
Renata Talar-Wojnarowska ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Sleep Quality ◽  
Sleep Fragmentation ◽  
Clinical Severity ◽  
Serotonin Level ◽  
Intestinal Physiology ◽  
Tnf Α

Abstract Background and aims Serotonin affects intestinal physiology, mood, as well as circadian rhythm. Moreover, serotonin has proinflammatory function. Therefore, the aim of this study was to investigate the role of serotonin in clinical severity of Crohn’s Disease (CD) and its effect on pain and sleep quality. Methods Fifty-nine CD patients (34 in exacerbation and 25 in remission according to the Harvey-Bradshaw Index-HBI) and 25 health control individuals(HC) were recruited. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and subjective severity of pain by the Visual Analog Scale (VAS). Seventeen patients were treated with anti-TNF-α induction therapy for 14 weeks. Results Serotonin level was higher in CD (145.12ng/mL, IQR:98.14–179.25) compared to HC (87.52ng/mL, IQR:70.04–129.39; p=0.002) and in exacerbation of CD (157.66ng/mL, IQR:111.94–197.64) compared to remission (122.33ng/mL, IQR:83.28–163.67; p=0.029). Serotonin level with cut-off point of 92.45 ng/mL is useful for distinguishing participants with CD from HC (sensitivity: 78%, specificity: 60%, positive predictive value: 82%). Positive correlation between serotonin and HBI (r=0.279, p=0.032) and severity of diarrhoea (r=0.260, p=0.047) were found. Serotonin does not correlate with PSQI (r=0.152, p=0.168), but correlates with presence of sleep fragmentation for example by getting up to use the bathroom (joined 5b-5j PSQI questions; r=0.270, p=0.039). Correlations between serotonin and VAS were also obtained (r=0.220, p=0.045). Moreover, serotonin level significantly decreased after anti-TNF-α therapy (192.35ng/mL, IQR:150.36–225.56 vs. 121.11ng/mL, IQR:91.28–188.87; p=0.006). The study was funded by National Science Centre, Poland (#2018/31/N/NZ5/03715). Conclusions Serotonin level correlates with the severity of CD and decreases after anti-TNF-α therapy. It is associated with sleep fragmentation, which may be caused by diarrhea.

scholarly journals Is Inflammation a Friend or Foe for Orthodontic Treatment?: Inflammation in Orthodontically Induced Inflammatory Root Resorption and Accelerating Tooth Movement

2021 ◽  
Vol 22 (5) ◽  
pp. 2388
Author(s):  
Masaru Yamaguchi ◽  
Shinichi Fukasawa
Keyword(s):  
Inflammatory Mediators ◽  
Orthodontic Treatment ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Root Resorption ◽  
Orthodontic Tooth Movement ◽  
Tnf Α ◽  
Orthodontic Forces ◽  
Necrosis Factor

The aim of this paper is to provide a review on the role of inflammation in orthodontically induced inflammatory root resorption (OIIRR) and accelerating orthodontic tooth movement (AOTM) in orthodontic treatment. Orthodontic tooth movement (OTM) is stimulated by remodeling of the periodontal ligament (PDL) and alveolar bone. These remodeling activities and tooth displacement are involved in the occurrence of an inflammatory process in the periodontium, in response to orthodontic forces. Inflammatory mediators such as prostaglandins (PGs), interleukins (Ils; IL-1, -6, -17), the tumor necrosis factor (TNF)-α superfamily, and receptor activator of nuclear factor (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) are increased in the PDL during OTM. OIIRR is one of the accidental symptoms, and inflammatory mediators have been detected in resorbed roots, PDL, and alveolar bone exposed to heavy orthodontic force. Therefore, these inflammatory mediators are involved with the occurrence of OIIRR during orthodontic tooth movement. On the contrary, regional accelerating phenomenon (RAP) occurs after fractures and surgery such as osteotomies or bone grafting, and bone healing is accelerated by increasing osteoclasts and osteoblasts. Recently, tooth movement after surgical procedures such as corticotomy, corticision, piezocision, and micro-osteoperforation might be accelerated by RAP, which increases the bone metabolism. Therefore, inflammation may be involved in accelerated OTM (AOTM). The knowledge of inflammation during orthodontic treatment could be used in preventing OIIRR and AOTM.

ROLE OF INTER LEUKIN 10 AND TUMOR NECROSIS FACTOR-ΑLPHA IN PANCREATITIS

2021 ◽  
pp. 14-17
Author(s):  
Mukherjee.J. R ◽  
Mukherjee. B ◽  
Roy. S ◽  
Jana. D ◽  
Bandopadhyay. S ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
General Surgery ◽  
Tumor Necrosis ◽  
Cell Injury ◽  
Gall Stone ◽  
Tnf Alpha ◽  
Tnf Α ◽  
The Mean ◽  
Necrosis Factor

Background: Pancreatic acinar cell injury triggers the synthesis and release of pro-inammatory cytokines and chemokines. The involvement of several pro-inammatory and anti-inammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33 and tumor necrosis factor-α is involved in the pathogenesis of pancreatitis. Aim: This study aims to validate the role of activation of TNF-alpha and IL-10 as a biomaker marker in patients with Pancreatitis in Indian subcontinent.Material and methods: 50 Patients of Pancreatitis attending general surgery OPD and admitted to General Surgery department of SSKM Hospital, Kolkata, West Bengal, India were taken. Result: It was found that in alcoholic, the mean TNF - α (mean±s.d.) of the patients was 19.4027 ± 8.3275 pg/ml. In ascites, the mean TNF - α (mean±s.d.) of the patients was 19.9767 ± 2804 pg/ml. In chronic, the mean TNF - α (mean±s.d.) of the patients was 18.8533 ± 8.4674 pg/ml. In gall stone, the mean TNF - α (mean±s.d.) of the patients was 16.3421 ± 9.9499 pg/ml. In osteoarthritis, the mean TNF - α (mean±s.d.) of the patients was 12.4750 ± 8.3085 pg/ml. Distribution of mean TNF - α vs. association was not statistically signicant (p=0.7309).Conclusion: It was found that IL10 was higher in Ascites patients though it was not statistically signicant. TNF alpha was higher in Ascites patients. TNF alpha was higher in normal Pancreatitis.

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