scholarly journals Oligonucleotide Therapies in the Treatment of Inflammatory Joint Disease

Author(s):  
Susanne N Wijesinghe ◽  
Mark A Lindsay ◽  
Simon W Jones

Osteoarthritis and rheumatoid arthritis are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both osteoarthritis and rheumatoid arthritis involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in osteoarthritis. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 902
Author(s):  
Susanne N. Wijesinghe ◽  
Mark A. Lindsay ◽  
Simon W. Jones

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.


2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Zhongbin Xia ◽  
Fanru Meng ◽  
Ying Liu ◽  
Yuxuan Fang ◽  
Xia Wu ◽  
...  

Background: Rheumatoid arthritis (RA) is a inflammatory disease that characterized with the destruction of synovial joint, which could induce disability. Inflammatory response mediated the RA. It has been reported that MiR-128-3p is significantly increased in RA, while the potential role was still unclear. Methods: T cells in peripheral blood mononuclear cell (PBMC) were isolated from the peripheral blood from people of RA and normal person were used. Real-time PCR was performed to detect the expression of MiR-128-3p, while the protein expression of tumor necrosis factor-α-induced protein 3 (TNFAIP3) was determined using Western blot. The levels of IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). The expression of CD69 and CD25 was detected using flow cytometry. The RA mouse model was constructed for verification of the role of MiR-128-3p. Results: The expression of MiR-128-3p was significantly increased, while TNFAIP3 was decreased, the levels of IL-6 and IL-17 were also increased in the T cells of RA patients. Down-regulated MiR-128-3p significantly suppressed the expression of p-IkBα and CD69, and CD25in T cells. MiR-128-3p targets TNFAIP3 to regulate its expression. MiR-128-3p knockdown significantly suppressed the activity of nuclear factor κB (NF-κB) and T cells by up-regulating TNFAIP3, while cells co-transfected with si-TNFAIP3 abolished the effects of MiR-128-3p knockdown. The in vivo experiments verified the potential role of MiR-128-3p on RA. Conclusion: Down-regulated MiR-128-3p significantly suppressed the inflammation response of RA through suppressing the activity of NF-κB pathway, which was mediated by TNFAIP3.


Biomedicines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 9 ◽  
Author(s):  
Andrei A. Deviatkin ◽  
Yulia A. Vakulenko ◽  
Ludmila V. Akhmadishina ◽  
Vadim V. Tarasov ◽  
Marina I. Beloukhova ◽  
...  

Rheumatoid arthritis (RA) is a systemic inflammatory joint disease affecting about 1% of the population worldwide. Current treatment approaches do not ensure a cure for every patient. Moreover, classical regimens are based on nontargeted systemic immune suppression and have significant side effects. Biological treatment has advanced considerably but efficacy and specificity issues remain. Gene therapy is one of the potential future directions for RA therapy, which is rapidly developing. Several gene therapy trials done so far have been of moderate success, but experimental and genetics studies have yielded novel targets. As a result, the arsenal of gene therapy tools keeps growing. Currently, both viral and nonviral delivery systems are used for RA therapy. Herein, we review recent approaches for RA gene therapy.


2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ilaria Floris ◽  
Víctor García-González ◽  
Belen Palomares ◽  
Kurt Appel ◽  
Beatrice Lejeune

Background. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damages as well as pain and disability. In order to prevent disease progression, reduce pain, and major symptoms of RA, one good strategy consists in targeting proinflammatory cytokines that have the key role in the vicious circle of synovial inflammation and pain. The micro-immunotherapy medicine (MIM) 2LARTH® targets cytokines involved in inflammation. Aim. The aim of the study is to evaluate the effect of the MIM compared to vehicle in an in vivo model of RA, induced in mice after immunization with articular bovine type II collagen. Methods. Vehicle and MIM were dissolved in pure water (1 capsule in 100 ml) and 100 µl was given by gavage daily for 14 days. To evaluate the severity of arthritis, wrist and ankle thickness was determined, paw edema was measured, and a clinical score from 0 to 4 was established. Furthermore, histological analysis was performed. To evaluate systemic inflammation, circulating levels of IL-1β and TNF-α were measured by ELISA. Results. Ankle thickness was found to be significantly reduced in MIM-treated mice compared to vehicle-treated mice (P<0.05) and compared to untreated me (P<0.01). Paw edema was reduced, as well as clinical score attributed to MIM-treated mice in comparison with vehicle-treated mice and untreated CIA mice (P<0.01). In line with these results, histological analysis confirmed that MIM reduced inflammation and joint destruction in comparison to controls. No significant changes were found in plasmatic IL-1β levels between CIA and controls, while the levels of TNF-α significantly increased in the CIA group, and were lowered in MIM-treated mice (P<0.05 vs. vehicle and vs. CIA). Conclusion. The results indicate that the tested medicine reduces inflammation, histological, and clinical signs of RA in a CIA model.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Sarah Dörenkamp ◽  
Ilse Mesters ◽  
Rein Vos ◽  
Jan Schepers ◽  
Marjan van den Akker ◽  
...  

Little is known about whether and how two chronic diseases interact with each other in modifying the risk of physical inactivity. The aim of the present study is to identify chronic disease pairs that are associated with compliance or noncompliance with the Dutch PA guideline recommendation and to study whether specific chronic disease pairs indicate an extra effect on top of the effects of the diseases individually. Cross-sectional data from 3,386 participants of cohort study SMILE were used and logistic regression analysis was performed to study the joint effect of the two diseases of each chronic disease pair for compliance with the Dutch PA guideline. For six chronic disease pairs, patients suffering from both diseases belonging to these disease pairs in question show a higher probability of noncompliance to the Dutch PA guideline, compared to what one would expect based on the effects of each of the two diseases alone. These six chronic disease pairs were chronic respiratory disease and severe back problems; migraine and inflammatory joint disease; chronic respiratory disease and severe kidney disease; chronic respiratory disease and inflammatory joint disease; inflammatory joint disease and rheumatoid arthritis; and rheumatoid arthritis and osteoarthritis of the knees, hips, and hands.


Author(s):  
Verônica Assalin Zorgetto-Pinheiro ◽  
Alexandre Meira de Vasconcelos ◽  
Rafael Sanaiotte Pinheiro ◽  
Danielle Bogo ◽  
Iandara Schettert Silva

Rheumatoid arthritis is an autoimmune and chronic pathological condition characterized by an inflammatory process of the joints It is a complex and multifactorial, involving genetic, epigenetic and environmental factors and the use of experimental models is required to better understand its pathology and for drug testing. The aim of this study was to perform a systematic literature review on experimental models in rheumatoid arthritis using IRAMUTEQ, a software that analysis, qualitatively and quantitatively, text fragments, as a methodological tool. After searching for articles published in the last five years on Scopus database and applying the exclusion criteria, we ended with 84 articles. The most commonly employed experimental models was the arthritis induction by inoculation of the Complete Freund's Adjuvant (CFA), followed by the use of combined methodologies and the collagen-induced arthritis (CIA). The analyses of abstracts by the IRAMUTEQ software provided a classification according to their textual elements in four classes, which were grouped into three main themes: in vivo models (class 1), clinical practice and traditional medicine (classes 2 and 3) and in vitro models (class 4) and it was also possible to build a similarity tree of the terms present in the abstracts and a word cloud with the most cited terms. Thus, the use of the IRAMUTEQ software as a methodological tool has been satisfactory, since it was possible to identify the main experimental models used, keywords, pathological processes and molecules involved in the pathogenesis of rheumatoid arthritis free of the researchers’ bias, in addition to being a tool for visual and intuitive results.


2021 ◽  
Vol 2 (1) ◽  
pp. 25-32
Author(s):  
Danilo Jeremić ◽  
Boris Gluščević ◽  
Stanislav Rajković ◽  
Želimir Jovanović ◽  
Branislav Krivokapić

Osteoarthritis, osteoarthrosis, and osteoarthropathy are diseases that doctors encounter daily in their practice. The use of all three terms is customary, often without a clear justification as to why a particular term is used for a particular case. In the past several decades, doctors mainly differentiated among these diseases based on clinical presentation and radiography. In the past several years, however, significant progress has been made in the field of biochemical, immunological, and cytohistological research, which has provided explanations for the pathogenesis of these conditions, enabled defining differences amongst them and facilitated the use of appropriate terms for each one of these diseases. The term arthritis (osteoarthritis) should be used exclusively for primarily inflammatory joint diseases-rheumatoid arthritis, juvenile arthritis, reactive arthritis (Reiter's syndrome). If the etiology is infectious, this must also be emphasized-septic (purulent) arthritis, tuberculous arthritis. Arthrosis (osteoarthrosis) relates to changes in the joints occurring due to pathological processes within the joint itself, but which, in their basis, are not inflammatory. Arthropathy is a term for joint disease stemming from another diseased organ or system of organs.


2021 ◽  
Author(s):  
Fatemeh Owlia ◽  
Shabnam Sohanian ◽  
Elnaz Karimian ◽  
Maryam Jalili Sadrabad

Abstract Introduction: Rheumatoid Arthritis (RA) is the most common chronic inflammatory joint disease. Periodontitis is also an inflammatory disease that affects the periodontal tissue. The former studies have been suggested probable relationship between them. Objectives: The purpose of this study was to evaluate the relation of severity of Periodontitis and RA activity. Materials and Methods: In this study 50 patients who referred to the Rheumatology Department of the Khatamolanbia clinic of Yazd considering inclusion criteria were enrolled in the study. After obtaining the informed consent, based on rheumatologic criteria such as Sedimentation (ESR and Clinical features they were divided into two groups; active and inactive RA. Topics were compared based on age, sex, Rheumatoid Factor, Erythrocyte Sedimentation Rate, Hemoglobin Level for RA Bleeding on Probing, Clinical Attachment Loss, Pocket Depth, and Tooth Loss for periodontitis. Results: The results of this study showed that there was no significant relationship between the variables studied in the active and inactive RA subgroups (p> 0.05). Conclusion: According to the present study while all RA patients show some degree of periodontitis, the periodontitis severity is not correlated with RA activity.


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