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ID PMID Title PublicationDate abstract
31583550 Ocular manifestations of rheumatic diseases. 2020 Feb PURPOSE: Our aim was to summarize key aspects of the pathomechanism and the ocular involvements of rheumatic and systemic autoimmune diseases. METHODS: Apart from a paper in French (Morax V, Ann Oculist 109:368-370, 1893), all papers referred to in this article were published in English. All the materials were peer-reviewed full-text papers, letters, reviews, or book chapters obtained through a literature search of the PubMed database using the keywords ocular manifestations; pathogenesis; systemic inflammatory rheumatic diseases; rheumatoid arthritis; osteoarthritis; fibromyalgia; systemic lupus erythematosus; seronegative spondyloarthritis; ankylosing spondylitis; reactive arthritis; enteropathic arthritis; psoriatic arthritis; systemic sclerosis; polymyalgia rheumatica and covering all years available. Some statements articulated in this paper reflect the clinical experience of the authors in their tertiary-referral center. RESULTS: Ophthalmic disorders are categorized by anatomical subgroups in all rheumatic diseases. The most common ocular manifestations are diverse types of inflammations of different tissues and dry eye disease (DED). CONCLUSION: The eye could be a responsive marker for the onset or aggravation of an immune reactivation in many rheumatic diseases, furthermore, ocular findings can antedate the diagnosis of the underlying rheumatic disease. By recognizing ocular manifestations of systemic rheumatic diseases it might be possible to avoid or at least delay many long term sequelae.
32485832 Metabolomic Profiling in the Characterization of Degenerative Bone and Joint Diseases. 2020 May 29 Osteoarthritis and inflammatory arthropathies are a cause of significant morbidity globally. New research elucidating the metabolic derangements associated with a variety of bone and joint disorders implicates various local and systemic metabolites, which further elucidate the underlying molecular mechanisms associated with these destructive disease processes. In osteoarthritis, atty acid metabolism has been implicated in disease development, both locally and systemically. Several series of rheumatoid arthritis patients have demonstrated overlapping trends related to histidine and glyceric acid, while other series showed similar results of increased cholesterol and glutamic acid. Studies comparing osteoarthritis and rheumatoid arthritis reported elevated gluconic acid and glycolytic- and tricarboxylic acid-related substrates in patients with osteoarthritis, while lysosphingolipids and cardiolipins were elevated only in patients with rheumatoid arthritis. Other bone and joint disorders, including osteonecrosis, intervertebral disc degeneration, and osteoporosis, also showed significant alterations in metabolic processes. The identification of the molecular mechanisms of osteoarthritis and inflammatory arthropathies via metabolomics-based workflows may allow for the development of new therapeutic targets to improve the quality of life in these patient populations.
32258008 Efficient Delivery of Triptolide Plus a miR-30-5p Inhibitor Through the Use of Near Infrar 2020 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease for which treatment focuses on suppressing an overactive immune system and maintaining the physiological balance of synovial fibroblasts (SFs). We found that miR-30-5p was highly expressed in rheumatoid arthritis synovial fibroblasts (RASFs). Subsequently, we predicted that phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2) might be a putative target of miR-30-5p. Recent studies have reported that PIK3R2 can maintain the physiological homeostasis of RASFs. Therefore, miR-30-5p inhibitor has the potential to be used in the treatment of RA, but low levels of miR-30-5p inhibitor internalization affect its application. Triptolide (TP) is an effective drug in the treatment of RA but induces severe toxicity and has a narrow therapeutic window. In this study, the cell internalization performance of miR-30-5p inhibitor was improved by loading it into cell membrane penetrating peptide (CADY)-modified mesoporous silica nanoparticles (MSNs), and the toxicity of TP was decreased by loading it into a controlled drug release system based on MSNs. The nanodrug carrier was constructed by filling a phase-change material (PCM) of 1-tetradecanol and drugs into MSNs that could be triggered by an NIR laser with thermo-chemo combination RA therapy. Our results show that the miR-30-5p inhibitor-loaded MSNs@CADY significantly inhibited RASF proliferation and increased apoptosis. In addition, MSNs@PCM@TP under 808 nm laser irradiation were effective in downregulating immune system activation in an RA rat model. Finally, the results of a pharmacodynamics study showed that the combination of MSNs@CADY@miR-30-5p inhibitor and MSNs@PCM@TP under 808 nm laser significantly increased the effectiveness of RA treatment. These findings provide a novel understanding of RA pathogenesis and a theoretical basis for RA treatment.
34046570 Knowledge of cardiovascular disease risk in rheumatoid arthritis patients before and after 2021 Mar OBJECTIVES: This study aims to improve knowledge on cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients using a multi- language leaflet tailored to our multi-ethnic patient population. PATIENTS AND METHODS: This was a prospective study conducted in Hospital Pulau Pinang, Malaysia, between March 2015 and June 2015. Educational intervention was provided to 96 patients (11 males, 85 females; mean age 52.4±12.9 years; range, 20 to 83 years) who fulfilled the inclusion/exclusion criteria. Questionnaires to assess knowledge of CVD risk were given to patients to be answered before reading the informative leaflet, after one hour of intervention, and during their next follow-up three months from the intervention. Both the informative leaflet and questionnaires were prepared in English and then translated into Malay and Chinese languages to suit the need of local patients. RESULTS: Our results showed that RA patients had good knowledge at baseline regarding risk of smoking, hypertension, and hyperlipidemia on increasing CVD risk and that exercise would not damage their joints. However, they had low knowledge at baseline regarding the amount of exercise needed for lower CVD risks and risk of CVD with use of anti-inflammatory drugs in RA. Total knowledge score increased significantly from baseline immediately after educational intervention. However, total knowledge score decreased after three months compared to immediate post- intervention phase while it was still significantly higher compared to baseline. The improvement was most obvious for knowledge regarding anti- inflammatory drugs and CVD risk and knowledge regarding the number of flares and CVD risk. Our study did not find any significant association between demographic characteristics and traditional cardiovascular risk factors with knowledge of CVD risk. CONCLUSION: Rheumatoid arthritis patients have low knowledge regarding their CVD risk related to their disease. The intervention of providing an informative leaflet effectively improved the knowledge of this group of patients on CVD risk particularly in the field related to RA-specific risk.
32308784 Modified Rheumatoid Arthritis Protocol for Rituximab in Pemphigus: A Retrospective Case Se 2020 Feb Background: Rituximab, an anticluster of differentation 20 antibody, has been shown in open series studies to be effective in treating pemphigus. In the literature, lymphoma (dose of 375mg/m(2), four-week infusion) and rheumatoid arthritis (two infusions of 1,000mg each, 15 days apart) are two protocols extensively used for rituximab treatment in pemphigus. Objective: We investigated whether a modified rheumatoid arthritis protocol, in which the patient received a single treatment course ranging from 2 to 5 infusions of 1,000mg of rituximab during an interval of four weeks is safe and effective in pemphigus management. Methods: Patients with pemphigus were treated with a single treatment course ranging from 2 to 5 infusions of 1,000mg of rituximab during an interval of four weeks. Clinical consensus late endpoints and desmoglein 1 and desmoglein 3 indices were monitored. Results: We enrolled 32 patients in the study: four with pemphigus foliaceus (PF) and 28 with pemphigus vulgaris (PV). The follow-up period was 98.22±20.65 weeks (range: 40-140 weeks). All 32 patients responded to therapy. Nineteen patients achieved complete remission during a median period of 46 weeks (8 on minimal therapy, 11 off therapy). Thirteen patients achieved partial remission during a median period of 46 weeks (8 on minimal therapy, 5 off therapy). Relapses were seen in five (15.63%) patients between 72 and 96 weeks (median: 96 weeks) after the start of therapy. The antidesmoglein index correlated well with clinical improvement in PV or PF. Conclusion: Modified rheumatic arthritis protocol for rituximab was shown to be effective and safe in treating patients with pemphigus.
32955629 Acute severe hepatitis in adult-onset Still's disease: case report and comprehensive revie 2021 Jun Acute severe hepatitis is a rare complication of adult-onset Still's disease (AOSD). This condition is poorly characterized. We performed a review of the medical literature to describe clinical, biological, pathological, and treatment characteristics from AOSD patients with acute severe hepatitis. Their characteristics were compared with AOSD patients without severe hepatitis. Twenty-one cases were collected including a new case reported here. Patients with severe hepatitis were mostly young adults with a median age of 28 years (range: 20 to 55 years). Overall, patients with severe hepatitis had less arthritis, macular rash, sore throat, lymphadenopathy, or splenomegaly than patients without severe hepatitis. Cytopenia was more frequent in case of severe hepatitis. Most patients were treated with steroids, and the use of biotherapies has increased over the last decade. Despite treatment, 49% of patients required liver transplantation and 24% died. Key Points • Acute severe hepatitis in adult-onset Still's disease (AOSD) is associated with liver transplantation and/or death in, respectively, 43% and 24% of cases. • Severe hepatitis is the inaugural manifestation of AOSD in half of cases. Diagnosis is difficult when extra-hepatic clinical manifestations are lacking. • The mechanism of hepatic necrosis in AOSD with severe hepatitis is unknown. Liver biopsy is not specific and should not delay treatment initiation.
31983549 [Purtscher-like retinopathy associated with adult onset still disease: Case report and rev 2020 Apr INTRODUCTION: Putscher-like retinopathy is a retinal disease that is similar to the syndrome initially described in 1910 by Purtscher, but occurring in a non-traumatic context. CASE REPORT: We describe a case of acute, Putscher-like retinopathy in a 48-year-old woman experiencing adult onset Still's disease. The diagnosis was based on fundus examination and fluorescein angiography. Based on a review of the literature, we discuss the current available data on the pathophysiology of this syndrome and its prognostic significance. The treatment remains controversial. CONCLUSION: When visual functional signs appear during adult Still's disease, it is necessary to evoke Putscher-like retinopathy, and to ask for an ophthalmological expertise.
32570239 Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Tes 2020 BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, swelling, and pain in the joints and involves systemic complications. Mouse models of RA have been extensively used to model the pathogenesis of RA and to develop effective therapies. Although many components of the immune system have been studied in these models, the role of crystallizable fragment (Fc) gamma receptors (FcγRs) in RA has been sorely neglected. The aim of this review was to introduce the different mouse models of RA and to describe the different drug development strategies that have been tested in these models to target FcγR function, with the focus being on drugs that have been made from the Fc of immunoglobulin G (IgG). SUMMARY: Evidence suggests that FcγRs play a major role in immune complex-induced inflammation in autoimmune diseases, such as RA. However, there is limited knowledge on the importance of FcγRs in the human disease even though there has been extensive work in mouse models of RA. Numerous mouse models of RA are available, with each model depicting certain aspects of the disease. Induced models of RA have nonspecific immune activation with cartilage-directed autoimmunity, whereas spontaneous models of RA develop without immunization, which results in a more chronic form of arthritis. These models have been used to test FcγR-targeting monoclonal antibodies, intravenous immunoglobulin (IVIg), subcutaneously administered IVIg, and recombinant Fcs for their ability to interact with and modify FcγR function. Recombinant Fcs avidly bind FcγRs and exhibit enhanced therapeutic efficacy in mouse models of RA. Key Message: The therapeutic utility of targeting FcγRs with recombinant Fcs is great and should be explored in human clinical trials for autoimmune diseases, such as RA.
32895357 Systemic juvenile idiopathic arthritis versus adult-onset Still´s disease: the pertinence 2020 Apr BACKGROUND: Systemic Juvenile Idiopathic Arthritis (sJIA) is a rare systemic inflammatory disease wich represents a subtype of a Juvenile Idiopathic Arthritis (JIA) according to the Classification of Edmonton. It is distinguished from other subtypes by its pathophysiology, systemic extra-articular involvement and treatment. This disease has strong similarities with Adult-onset Still`s Disease (AOSD). These diseases differing mainly in the diagnostic criteria. OBJECTIVE: To identify the similarities between sJIA and AOSD given the benefits that a change to the classification criteria would make. METHODS: Research Portuguese and English scientific papers in Pubmed database and published between 1992 and 2019 using the keywords "juvenile idiopathic arthritis"; "systemic juvenile idiopathic arthritis"; "Still´s disease" and "Adult-onset Still`s disease", having been selected the most clinically and historically relevant ones. RESULTS: The pathophysiology of SJIA has marked differences when compared to other subtypes of JIA, with a more prominent role of innate immunity and an increased production of interleukins (IL-1, IL-6 and IL-18). The sJIA presents several pathophysiological, clinical and analytical similarities with AOSD. Regarding the current diagnostic criteria (Edmonton´s for sJIA and Yamaguchi´s for AOSD), they differ mainly in the presence of arthritis, which is an essential criterion in the classification of Edmonton, while according to the classification of Yamaguchi, it is only required the presence of arthralgia. The requirement of arthritis in the initial presentation leads to delayed diagnosis in patients who present with other features of sJIA. Concerning treatment, new drugs are currently used in sJIA, allowing for a more oriented therapy in those systemic symptoms are the main problem in the long term. CONCLUSIONS: In a pathology associated to great mortality and morbidity as is sJIA, a timely diagnosis is essential, so a highly suggestive clinical history of sJIA, even in the absence of arthritis, can not be disregarded. Thus, a review of the criteria will allow a faster detection of the pathology in question and an earlier onset of the therapy aiming at a better prognosis.
33093874 Indications and outcome in total elbow arthroplasty: A systematic review. 2020 Oct BACKGROUND: Total elbow arthroplasty (TEA) is the established treatment for end-stage rheumatoid arthritis but improved surgical techniques have resulted in expanded indications. The aim of this study is to review the literature to evaluate the evolution of surgical indications for TEA. METHODS: A systematic review of PubMed and EMBASE databases was conducted. Case series and comparative studies reporting results after three types of primary TEA were eligible for inclusion. RESULTS: Forty-nine eligible studies were identified (n = 1995). The number of TEA cases published annually increased from 6 cases in 1980 to 135 cases in 2008. The commonest indication for TEA throughout the review period was rheumatoid arthritis but its annual proportion reduced from 77% to 50%. The mean Mayo Elbow Performance Score significantly improved for all indications. Three comparative studies reported statistically improved functional outcomes in rheumatoid arthritis over the trauma sequelae group. Complication and revision rates varied; rheumatoid arthritis 5.2-30.9% and 11-13%, acute fracture 0-50% and 10-11%, trauma sequelae 14.2-50% and 0-30%, osteoarthritis 50% and 11%, respectively. DISCUSSION: TEA can provide functional improvements in inflammatory arthritis, acute fractures, trauma sequelae and miscellaneous indications. Long-term TEA survivorship appears satisfactory in rheumatoid arthritis and fracture cases; however, further research into alternative surgical indications is still required.
32151962 MLL1 promotes migration and invasion of fibroblast-like synoviocytes in rheumatoid arthrit 2020 Mar 6 Rheumatoid arthritis (RA) is the most common inflammatory arthritis and is a major cause of disability. Interestingly, the histone methyltransferase mixed-lineage leukemia 1 (MLL1) has been linked to many inflammation-related diseases. Moreover, toll-like receptor 4 (TLR4) has been reported to induce migration and invasion in RA-fibroblast-like synoviocytes (FLSs). This study intended to delineate the functional relevance of MLL1 in RA progression, which implicates the regulation of TLR4. First, clinical synovial tissues were collected from RA patients and patients with severe joint trauma to isolate FLSs. We identified highly expressed MLL1 and TLR4 in synovial tissues of RA patients, and the expression of them was positively correlated in RA-FLSs. More importantly, silencing of MLL1 and TLR4 resulted in suppressed migration and invasion of RA-FLSs, accompanied by reduced inflammation. Additionally, mechanistic investigations showed that MLL1 upregulated TLR4 expression by inducing H3K4me3 in the promoter region of TLR4. Functional assays revealed that overexpression of MLL1 activated the TRIF/NF-κB signaling pathway, resulting in accelerated migration and invasion, and inflammation of RA-FLSs in vitro. TLR4 knockdown could compromise the effects of MLL1 overexpression. The in vivo assays in a collagen-induced arthritis rat model validated the in vitro findings. Taken together, histone methyltransferase MLL1 induces TLR4 expression by mediating H3K4me3 in the TLR4 promoter, thus activating the TRIF/NF-κB signaling pathway, which thereby promotes the migration and invasion of RA-FLSs and ultimately exacerbates the progression of RA.
33850833 Periapical abscess progressing to parotitis and descending necrotizing mediastinitis with 2020 Oct Patients on Type 2 biologics, such as etanercept, are at increased risk for aggressive infections. This may be further exacerbated by concomitant systemic corticosteroid use or comorbidities such as diabetes. We report a case of a patient with rheumatoid arthritis on etanercept with poor dentition and periodontal disease, who developed parotitis with peritonsillar abscess and descending necrotizing mediastinitis (DNM) with periaortic abscess arising from a periapical abscess. Morbidity and mortality of such infections is high. A multimodal assessment and treatment team is required to optimize patient survival and outcomes. This manuscript discusses the diagnostic and treatment challenges of DNM of immunocompromised patients.
32509932 Sex differences in frailty and its association with low bone mineral density in rheumatoid 2020 Jun OBJECTIVES: Frailty in the general population is associated with poor health outcomes including low bone mass and osteoporotic fracture. The relationship between frailty and low bone mineral density (BMD) in rheumatoid arthritis (RA) is unknown. This study examined associations between frailty and BMD in RA, controlling for established osteoporosis risk factors. METHODS: We performed a cross-sectional analysis of a longitudinal RA cohort (n = 138; 117 female, 21 male). Participants fulfilled ACR RA classification criteria. Frailty was evaluated using the Fried Index, categorizing each participant as robust, pre-frail or frail. To identify independent predictors of BMD, we performed a multivariable linear regression analysis. Because risk factors for low BMD differ between sexes, we performed additional sex-stratified multivariable analyses. RESULTS: Mean age and disease duration were 58.0 ± 10.8 and 19 ± 10.9 years, respectively. The majority of participants were categorized as pre-frail (70%) or frail (10%). Females had higher rates of frailty than males. In the whole cohort, both pre-frail and frail had independent negative associations with BMD (β = -0.074 and -0.092 respectively, p < 0.05). In sex-stratified analyses, frailty did not have a significant association with BMD in females, but had a strong independent negative association in males (β = -0.247, p = 0.001). CONCLUSION: Frailty was associated with BMD in patients with RA. Females had higher rates of frailty than males, yet frailty was independently associated with BMD in males but not in females. Frailty appears to be an important factor associated with low BMD; sex may influence this relationship in RA.
33182050 IL-6 promotes collagen-induced arthritis by activating the NLRP3 inflammasome through the 2020 Nov Rheumatoid arthritis (RA) is an inflammatory disease with symmetric polyarthritis. IL-6 and NLRP3 inflammasome in macrophages contribute to the pathogenesis of RA. This study aimed to investigate the relationship between IL-6 and the NLRP3 inflammasome in RA. Here, we found that IL-6 inhibition reduced NLRP3 inflammasome activation in mice with collage-induced arthritis (CIA). In vitro studies showed that IL-6 directly induced NLRP3 inflammasome activation via cathepsin B (CTSB) in the presence of ATP. In addition, S100A9 induced by ATP stimulation promoted the interaction of CTSB and NLRP3 to activate the NLRP3 inflammasome. Our findings show a novel mechanism of NLRP3 inflammasome activation by IL-6 that may lead to a potential therapy for RA by interrupting the interaction between IL-6 and the NLRP3 inflammasome.
32184646 The Effect of Aqueous Extract of Trachyspermum ammi Seeds and Ibuprofen on Inflammatory Ge 2020 BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) is an inflammatory disease treated with nonsteroidal anti-inflammatory drugs that have different side effects. One of the plants used for this purpose in the traditional medicine is Trachyspermum ammi. The present study aimed at investigating the anti-inflammatory effect of this plant on type II collagen-induced arthritis (CIA) in Wistar rats. MATERIALS AND METHODS: The study was performed on 35 male Wistar rats. Seven rats were considered as the healthy control group (normal group), and CIA was stablished in the rest. The rats with a model of inflammatory arthritis were divided into four groups. One group did not receive any treatment and three groups were treated orally with ibuprofen (15 mg/kg), aqueous extract of the T. ammi seeds (100 mg/kg), or their combination for 30 days. The effect of different treatments was investigated on the paw thickness, arthritis score, and mRNA level of COX2 and iNOS genes. RESULTS: CIA increased paw thickness, arthritis score, and COX2 and iNOS mRNA levels compared to those of the normal group. Treatment with ibuprofen and aqueous extract alone or in combination reduced the studied variables. Reduction in the paw thickness, arthritis score, and iNOS mRNA level was more in the ibuprofen-treated group than the T. ammi extract-treated group, but treatment with T. ammi extract reduced COX2 mRNA level more than ibuprofen. CONCLUSION: It seems that the aqueous extract of T. ammi can be used alone or in combination with ibuprofen to treat RA.
32500508 Enhancement of an Auto-Injector Device for Self-Administration of Etanercept in Patients W 2020 Sep INTRODUCTION: Etanercept is effective in the management of rheumatoid arthritis (RA) and can be self-administered via an auto-injector. While these devices are generally well accepted, some patients are not comfortable with the process of self-administration; this has been cited as a reason for discontinuation of biologic treatment. Alternative routes of administration (e.g., infusion) are more resource intensive. The aim of this analysis was to explore the attributes of auto-injection devices that impact patient confidence and ability to self-administer. METHODS: Patients with RA (n = 168) and healthcare providers (n = 82) in Belgium, Germany, Japan, Spain, and the UK were interviewed (n = 250 overall). Mock injection procedures were carried out using an auto-injector device with the addition of a sleeve with a wider rubber grip. Importance of and performance of the device against a range attributes were captured using a Likert scale (1-7). Disease severity was captured using the Cochin hand function scale. RESULTS: Device attributes reported by patients to be most important were 'use without assistance' 'ease of administration', 'ease of operation', and 'ease of grip'. The device with additional sleeve performed strongly against these attributes, scoring 6.9 (out of 7), 6.8, 6.8, and 6.6, respectively with no difference observed between countries. Nurses and physicians reported similar responses. Qualitatively, patients reported that stability and grip provided a sense of control and reduced anxiety. Similar overall 'ease of operation' was reported between patients with mild (n = 89) or moderate/severe (n = 71) disease (score 6.4 vs. 6.5, respectively). CONCLUSIONS: The auto-injector plus sleeve performed strongly against key attributes even in patients with moderate/severe RA and patients with reduced grip strength. The robust grip improved patient confidence and reduced injection-related anxiety. This may be beneficial in patients who are anxious about self-administration, those new to self-administration, and potentially in patients with reduced hand dexterity as a result of either advanced disease or a painful day.
32322152 Cervical Pannus Without Rheumatoid Arthritis or Trauma. 2020 Apr Although usually seen in patients with rheumatoid arthritis, cervical pannus also can develop in patients who have had spine surgery.
32820356 Dental age estimation in children affected by juvenile rheumatoid arthritis. 2021 Mar Dental root calcification has proven to be a reliable biological evidence to estimate chronological age of children. The development of structures usually examined in the age estimation forensic practice (e.g. skeleton, teeth) is supposed to be influenced by diseases and nutritional, environmental, ethnic, and ultimately even socioeconomic factors. This research aims to study the age estimation in children affected by juvenile rheumatoid arthritis (JRA) with and without steroids treatment and compared with healthy subjects. MATERIAL AND METHODS: Dental age estimations based on 752 OPGs, 420 girls and 332 boys, aged from 3.3 to 15.99 years, were provided by applying Demirjian and Willems' original methods. Of the whole sample, 103 individuals were affected by JRA and 40 received a continuous corticosteroid therapy, over 1 year long. CONCLUSIONS: Willems' and Demirjian's original methods, as methods commonly applied to estimate age for sub-adults with unremarkable medical history, can be used for medico-legal purposes to children affected by JRA. Willems' method tended to underestimate age while Demirjian's method resulted to be prone to overestimation for both healthy and JRA-affected children. JRA showed to have no influence on root calcification process even in children that received steroid treatment for 1 year or longer.
33304967 RNA sequencing data from osteochondroprogenitor populations in synovial joints of mice dur 2020 Dec The aim of this study was to analyze the transcriptome of TER119(-)CD31(-)CD45(-)CD51(+)CD200(+)CD105(-) population (further, CD200(+)), potential early osteocondroprogenitors, whose frequency is reduced in the joints of mice with antigen-induced arthritis (AIA) [1]. A population defined by similar surface markers has been previously identified as murine skeletal stem cells in bone [2]. In order to confirm their identity this population was compared to TER119(-)CD31(-)CD45(-)CD51(+)CD200(-)CD105(+) (further, CD105(+)) cells, which possibly represent committed progenitors, or other non-progenitor population such as synovial fibroblasts. In order to asses changes in CD200+ population in inflammatory setting, it was also compared to the same population from healthy mice. AIA was induced by immunization of mice with methylated bovine serum albumin (mBSA) and subsequent intra-articular injection of mBSA, while non-immunized mice were injected with phosphate-buffered saline at all timepoints. Ten days after intra-articular injection, knee joints were harvested and synovial cells were released by collagenase digestion. Using fluorescence-activated cell sorting, 200-500 cells from selected populations were sorted directly into cell lysis buffer, RNA was reversely transcribed, and first strand cDNA product was amplified. cDNA amplicons were used for library preparation. Bioinformatics analysis was performed using cutadapt [3], HISAT2 [4], Samtools [5] and StringTie [6] tools, and egdeR [7], limma [8], and ClusterProfiler [9] Bioconductor packages. In addition to access to raw data at the NCBI Gene Expression Omnibus repository, this article also provides sample similarity analysis, tables of differentially expressed genes, graphic visualisations of differential expression and gene set enrichment analysis performed on publicly available GO terms. Interpretation of osteochondroprogenitor phenotype of CD200(+) population based on analysis of presented data is provided in the article "What do we know about bone morphogenetic proteins and osteochondroprogenitors in inflammatory conditions?" [10]. Reuse of this data may help researchers elucidate alterations of synovial stromal and osteochondroprogenitor populations in inflammatory settings and define their role in structural damage in rheumatoid arthritis.
32432116 Hi-JAKi-ng Synovial Fibroblasts in Inflammatory Arthritis With JAK Inhibitors. 2020 The Janus kinase (JAK)-Signal transducer and activator of transcription (STAT) pathway is one of the central signaling hubs in inflammatory, immune and cancer cells. Inhibiting the JAK-STAT pathway with JAK inhibitors (jakinibs) constitutes an important therapeutic strategy in cancer and chronic inflammatory diseases like rheumatoid arthritis (RA). FDA has approved different jakinibs for the treatment of RA, including tofacitinib, baricitinib and upadacitinib, and several jakinibs are being tested in clinical trials. Here, we reviewed published studies of jakinib effects on resolving synovial pathology in inflammatory arthritis. We discussed the results of jakinibs on structural joint damage in clinical trials and explored the effects of jakinibs across different in vitro, ex vivo, and in vivo synovial experimental models. We delved rigorously into experimental designs of in vitro fibroblast studies, deconvoluted jakinib efficacy in synovial fibroblasts across diverse experimental conditions and discussed their translatability in vivo. Synovial fibroblasts can readily activate the JAK-STAT signaling pathway in response to cytokine stimulation. We highlighted rather limited effects of jakinibs on the in vitro cultured synovial fibroblasts and inferred that direct and indirect (immune cell-dependent) actions of jakinibs are required to curb the fibroblast pathology in vivo. These actions have not been mimicked optimally in current in vitro experimental designs, where inflammatory stimuli do not naturally clear out with treatment as they do in vivo. While summarizing the broad knowledge of synovial jakinib effects, our review uniquely challenges future study designs to better mimick the jakinib actions in broader cell communities, as occurring in vivo in the inflamed synovium. This can deepen our understanding of collective synovial activities of jakinibs and their therapeutic limitations, thereby fostering jakinib development in arthritis.