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ID PMID Title PublicationDate abstract
26841182 [Methotrexate - anchor drug in the treament of rheumatoid arthritis]. 2016 Feb Methotrexate is in the centre of the treatment of rheumatoid arthritis. There are new insights in the understanding of its mechanism: intracellular polyglutamation activates the methotrexate molecule. The magnitude of this step is associated with response to the treatment. Further on, it was found that even low doses of methotrexate are sufficient to guarantee its effect as comedication of TNF-inhibitors. Finally, from the follow-up of long term cohorts it seems that methotrexate reduces mortality in rheumatoid arthritis independently from its effect on disease activity.
27133486 Patient-Reported Outcomes in Rheumatoid Arthritis. 2016 May Patient-reported outcomes (PROs) and their measures have a long and important history for determining the status and treatment of patients with rheumatoid arthritis (RA). This article describes the history and evolution of PROs for RA and the current state of the field, with key examples of accepted and widely used measures, and offers some reflection on the roles of PROs for the study and management of RA.
27558858 Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Di 2016 Sep BACKGROUND: Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). METHODS: Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes. FINDINGS: We identified three types of treatment response trajectories: 'gradual responders' (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; 'rapid responders' (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; 'inadequate responders' (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p=0.03), and EULAR good or moderate responses at 1year was much higher among 'rapid responders' (p<0.001). INTERPRETATION: Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.
27318499 Arthroscopic synovectomy of the knee in rheumatoid arthritis defined by the 2010 ACR/EULAR 2016 Oct BACKGROUND: The aims of this study were: (1) to evaluate the mid-term results and survivorship of arthroscopic synovectomy (AS) of the knee in rheumatoid arthritis (RA) defined with the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria; and (2) to identify prognostic factors. METHODS: Patients matching the 2010 ACR/EULAR criteria, with symptomatic knee synovitis for at least six months, treated with arthroscopic synovectomy of the knee at a minimum of three year followup were included. Pre-operative evaluation included Larsen, HAQ, DAS28, and Laurin scores. Post-operatively, Laurin, WOMAC, and patient satisfaction scores were evaluated. Different variables were investigated to find associations with the outcomes. Kaplan-Meier survival analysis was performed. RESULTS: Sixty-four patients met the inclusion criteria. Seven patients (9.6%) were lost to followup, leaving 57 patients (66 knees) for the present study. The average followup was 96.3months (SD 41). The pre-operative Laurin score was 3.91 points (SD 1.3) and significantly (P<0.001) improved after surgery (mean 8.2, SD 2). The post-operative average WOMAC score was 73.9 points (SD 45.9). Eighteen knees (27.3%) underwent revision procedures at an average of 48.6 months (SD 39.8). Joint degeneration (Larsen grade III) and range of movement (ROM) reduction (>10%) were identified as negative prognostic factors. Kaplan-Meier survivorship with total knee replacement as endpoint was: 78% at one year, 28% at four years, and six percent at 10 years. CONCLUSIONS: Although AS of the knee has still a role as a salvage procedure in the treatment of RA synovitis with initial joint degeneration (less than Larsen grade III) and good ROM, high revision rates and limited survivorship are reported.
26847108 A prospective, single-centre, randomised study evaluating the clinical, imaging and immuno 2016 Feb 5 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis, with significant impact on quality of life and functional status. Whilst biologic disease modifying anti-rheumatic drugs (bDMARD) such as tumour necrosis factor-inhibitor (TNFi) agents have revolutionised outcomes in RA, early diagnosis with immediate conventional therapy, titrated in a treat to target approach is also associated with high remission rates. The main aim of the VEDERA study (Very Early versus Delayed Etanercept in Rheumatoid Arthritis) is to assess the depth of remission, sustainability of remission and immunological normalisation induced by very early TNFi with etanercept (ETN) or standard of care +/- delayed ETN. METHODS/DESIGN: VEDERA is a pragmatic, phase IV single-centre open-label randomised superiority trial of 120 patients with early, treatment-naive RA. Patients will be randomised 1:1 to first-line ETN and methotrexate (MTX) or MTX with additional synthetic disease modifying anti-rheumatic drugs (sDMARDs) according to a treat to target (TT) protocol with further step up to ETN and MTX after 24 weeks if remission is not achieved. Participants will have regular disease activity assessments and imaging evaluation including musculoskeletal ultrasound and MRI. The main objective of this study is to assess the proportion of patients with early RA that achieve clinical remission at 48 weeks, following either treatment strategy. In addition, the participants are invited to take part in a cardio-vascular sub-study (Coronary Artery Disease in RA, CADERA), which aims to identify the incidence of cardiovascular abnormalities in early RA. DISCUSSION: The hypothesis underlining this study is that very early treatment with first-line ETN increases the proportion of patients with rheumatoid arthritis achieving clinical remission, in comparison to conventional therapy. TRIAL REGISTRATION: NCT02433184 , 23/04/2015.
27368008 Increased incidence of rheumatoid arthritis in multiple sclerosis: A nationwide cohort stu 2016 Jun Past studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness.A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01-2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24-2.56, P = 0.002).In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history.
26711868 Adipose-derived mesenchymal stem cells from infrapatellar fat pad of patients with rheumat 2016 Adipose-derived mesenchymal stem cells (ASCs) possess immunosuppressive properties, but their activity is dependent on stimuli provided by local environment. It is possible that proinflammatory milieu of rheumatoid joint affects ASCs function. To verify this hypothesis, rheumatoid ASCs (RA-ASCs) and osteoarthritic ASCs (OA-ASCs) derived from infrapatellar fat pad (IPFP) of the knee joint have been compared. RA- and OA-ASCs isolated from patients were cultured in vitro. Their secretory and proliferative activity was measured. Peripheral blood mononuclear cells (PBMCs) from healthy donors were co-cultured with ASCs. Then, PBMCs proliferation was measured by (3)H-thymidine incorporation method, cytokines secretion by immunoassays, T cells activation and regulatory T cells (Tregs) percentage - by flow cytometry. RA- and OA-ASCs properties in vitro were comparable, however, some differences in secretory activity occurred. RA- and OA-ASCs inhibited PBMCs proliferation and induced interleukin 10 production but up-regulated interleukin 17 A secretion and failed to limit release of other proinflammatory mediators (tumor necrosis factor [TNF], interferon γ [IFNγ], CCL5) by PBMCs. RA- and OA-ASCs did not suppress activation markers expression on T cells and did not trigger Tregs expansion. The present study shows that IPFP-ASCs from RA and OA patients have comparable functions in vitro. Their immunosuppressive activity seems to be impaired comparing to available data.
25791728 The endocannabinoid system and its therapeutic implications in rheumatoid arthritis. 2015 May Since the discovery of the endogenous receptor for Δ(9)-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA). RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA. Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA. In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs. In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment.
26398458 Analysis of 65 Renal Biopsies From Patients With Rheumatoid Arthritis (1976-2015): Change 2015 Oct INTRODUCTION: No inherent renal lesions are known in rheumatoid arthritis (RA), but urinary abnormalities and renal dysfunction have been described. OBJECTIVE: First, we describe the histopathological findings of renal biopsies (RBs) in patients with RA and associated clinical manifestations. Second, we evaluated time evolution of RA and the relationship between drugs and renal disease. Last, we investigate whether changes in the management of RA from 1976 to 2015 influenced RBs indication, frequency, and type of histopathological findings. PATIENTS AND METHODS: This is a retrospective and observational study conducted at a university hospital from Argentina. Patients with a diagnosis of RA (ACR, 1987) and RBs between 1976 and 2015 were included. Sixty-five patients met the inclusion criteria. The histopathological findings and associated clinical manifestations were evaluated. Time evolution of RA and the relationship between drugs and renal disease were also determined. To clarify these issues, we characterized 3 groups according to changes in the management of RA: 1976-1989, 1990-2002, and 2003-2015. RESULTS: The most common histopathological finding was renal amyloidosis in 31% (n = 20), followed by mesangial glomerulonephritis in 18% (n = 12), membranous nephropathy in 17% (n = 11), extracapillary proliferative glomerulonephritis in 15% (n = 10), focal segmental glomerular sclerosis in 9% (n = 6), minimal change nephropathy in 5% (n = 3), and tubulointerstitial nephritis in 5% (n = 3). Time evolution of renal amyloidosis was significantly higher than other RBs (15 ± 12 vs 7 ± 6.5 years). Nephrotic syndrome was the most common clinical manifestation (60%) followed by hematuria (46%) with or without proteinuria. Membranous nephropathy was related to the use of gold salts in 45% of cases, and its frequency decreased since 1990. Before 2003, renal amyloidosis was the leading cause of kidney disease, but mesangial glomerulonephritis reached the same frequency between 2003 and 2015. We found that RBs decreased 20% in the second period (1990-2002) and 40% in the last period (2003-2015). Nephrotic syndrome remained the main RB indication during the entire study period. CONCLUSION: This is the first report on RBs findings in patients with RA from Latin America. We found a significant reduction in RBs frequency and modified histological patterns throughout the study period, although RB indication was not modified. Changes in the management of RA might have influenced these findings.
27206918 Optimization of Folate-Targeted Immunotherapy for the Treatment of Experimental Arthritis. 2016 Aug Folate-targeted immunotherapy constitutes a powerful method for the treatment of established arthritis in multiple animal models of the disease. The therapy involves immunization of the animal against a hapten to induce anti-hapten antibodies, followed by injection with a folate-hapten conjugate to decorate the surface of folate receptor-positive (activated) macrophages with the antigenic hapten. The hapten-marked macrophages are then recognized by the anti-hapten antibodies and eliminated by immune mechanisms, leading to attenuation of disease symptoms. In the following paper, we optimize the therapy for elimination of inflammatory macrophages and suppression of rheumatoid arthritis symptoms. We also demonstrate a tight correlation between folate receptor-positive macrophage abundance in the liver and inflammation of affected joints. The results suggest that therapies that reduce folate receptor-positive macrophage populations in the body should constitute effective treatments for rheumatoid arthritis.
26683997 TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity o 2016 Jan 1 Rheumatoid arthritis (RA) is an immune-mediated disease with a pathogenesis that involves CD4 T cell activation. Multiple immune regulatory molecules expressed on CD4(+) T cells were involved in RA pathogenesis. In this study, we investigated the role of T cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) in RA. The frequency of TIGIT-positive CD4(+) T cells in the synovial fluid (SF) of active RA patients was lower than that of inactive RA patients. And a negative correlation between RA disease activity and TIGIT expression was found. In CD4(+) T cells isolated from SF of active RA patients, TIGIT upregulation significantly decreased cell proliferation, as shown by MTT assay. TIGIT overexpression also significantly decreased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR. In CD4(+) T cells isolated from SF of inactive RA patients, TIGIT was silenced by siRNA transfection. As expected, TIGIT knockdown resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. A RA mouse model was established using type II collagen induction. TIGIT was upregulated in RA mouse by lentivector infection. As expected, TIGIT overexpression in vivo significantly alleviated the disease severity and deceased the levels of anti-collagen II antibodies. TIGIT upregulation in the early stage was more effective to alleviate disease severity. Our data suggested the potential therapeutic role of TIGIT in RA patients.
25291242 Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, di 2016 Mar AIM: To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity. METHODS: The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS-28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25-OH-vitamin D was measured in patients and controls. RESULTS: The patients' mean age was 41.59 ± 9.69 years and disease duration 5.89 ± 3.67 years. The level of vitamin D in RA patients was significantly lower (23.11 ± 12.71 ng/mL) than that in the controls (32.59 ± 13.06 ng/mL) (P = 0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n = 33) had significantly lower levels of vitamin D (19.08 ± 10.59 ng/mL) than those without (27.55 ± 13.51 ng/mL) (P = 0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39 ± 7.84 ng/mL) to those not (31.85 ± 13.85 ng/mL) (P < 0.001). Vitamin D significantly correlated with QoL index (r = 0.58, P < 0.001) and negatively with HAQ II (r = -0.36, P = 0.004) and BMI (r = -0.39, P = 0.001). CONCLUSION: Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium.
26523019 Rheumatoid Arthritis: Trends in Antirheumatic Drug Use, C-reactive Protein Levels, and Sur 2015 Dec OBJECTIVE: Over the past decade, the therapeutic approach used to treat patients with rheumatoid arthritis (RA) has considerably changed. It remains unclear whether these changes have been accompanied by decreased disease severity and surgical treatment burden at the population level. Therefore, we investigated time trends in antirheumatic drug consumption, C-reactive protein (CRP) levels, and use of orthopedic surgery among Danish patients with RA. METHODS: Using medical databases, we identified all patients with RA living in Northern Denmark during 1996-2012. For each calendar year, we computed the annual rate of antirheumatic drug use (1996-2010), the median CRP value in mg/l (1996-2011), and the proportions of patients who underwent hip replacement and other orthopedic procedures (1996-2012). RESULTS: Antirheumatic drug consumption per patient increased 5-fold, from 145.0 defined daily doses (DDD) in 1996 to 695.4 DDD in 2010. Median CRP declined from 20.5 mg/l [interquartile range (IQR), 10.0 to 43.5 mg/l] in 1996 to 10.0 mg/l (IQR, 4.2-17.8 mg/l) in 2011. From 1996 to 2012, declining proportions of patients with RA underwent hip replacement (14.9% to 10.1%) and other joint operations (29.1% to 23.4%), while the annual proportion of patients who underwent soft tissue procedures increased from 20.7% to 23.4%. CONCLUSION: Antirheumatic drug consumption has substantially increased among patients with RA since 1996, in association with reduced disease activity (i.e., lower CRP levels), fewer joint procedures (including hip replacements), and more soft tissue procedures.
26712499 High rates of obesity and greater associated disability among people with rheumatoid arthr 2016 Feb Obesity in rheumatoid arthritis has been associated with increased risk of comorbidities, larger medical costs, decreased quality of life, higher disease activity, and reduced therapeutic responses. We assessed the burden of obesity among rheumatoid arthritis patients and its impact on patient-reported outcomes. Patients receiving care at two Canadian University Centers were included. Height and weight were measured and selected sociodemographic and rheumatoid arthritis (RA) characteristics as well as patient-reported outcomes were obtained. Patients were classified according to WHO criteria and proposed RA cut points, and results were compared with national data. Using WHO criteria, 68 (34 %) RA patients were classified as obese (vs. ~25 % of Canadians). Using RA cut points, 112 (55 %) RA patients were classified as obese. With both classification methods, obese individuals had significantly higher mean HAQ scores and a higher odds of significant disability (HAQ ≥ 1: WHO OR 2.3; 95 % CI 1.2, 4.2 and RA-specific OR 1.8; 95 % CI 1.0, 3.2). Independent of the classification method use, RA patients have significantly higher rates of obesity than national prevalence estimates. Obese RA patients had about twice the odds of reporting moderate to severe disability.
25700648 [Modern disease-modifying antirheumatic drugs]. 2015 Mar The term modern disease-modifying antirheumatic drugs (DMARD) includes not only the constantly growing family of DMARDs for chronic inflammatory rheumatic diseases but also the repositioning of established drugs in updated and novel algorithms of the different entities. The usual precursor for these developments is rheumatoid arthritis for which completely revised and updated guidelines have been published not only in Germany but also on the European level. In addition, label extensions to existing drugs have been granted for connective tissue diseases and vasculitides, e.g. anti-CD20 antibodies for antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides and belimumab for systemic lupus erythematosus. Moreover, several novel drugs, especially of the biologics class, have been either introduced in clinical rheumatology or are close to being licensed and include ustekinumab for psoriatic arthritis, granulocyte growth inhibitors and janus kinase inhibitors for rheumatoid arthritis and atacicept for systemic lupus erythematosus. With the termination of the patent for several biologics, a new momentum also took place: the approval of the so-called biosimilars which has already initiated intensive discussions not only with respect to "similar" effects and side effects but also with respect to their potential impact on economical aspects.
27608796 Evaluation of Th9 lymphocytes in peripheral blood of rheumatoid arthritis patients and cor 2016 Sep 9 The aim of this study was to determine the prevalence of T helper 9 (Th9) lymphocytes in rheumatoid arthritis (RA) patients and to identify a possible association between the percentage of Th9 and the discontinuation of a biological treatment with an anti-tumor necrosis factor (TNF) (infliximab). We collected peripheral blood mononuclear cells (PBMCs) from 55 consecutive RA outpatients and 10 healthy controls. Among RA patients, 15 were not receiving any immunosuppressive drug, 20 were successfully treated with infliximab and 20 discontinued infliximab because of adverse events or inefficacy and were treated with other biological agents. PBMCs were cultured with/without infliximab 50 mg/L for 18 h, and the percentage of Th9 cells was assessed by means of flow cytometry. Th9 lymphocytes were identified as interferon gamma, interleukin (IL)4-, IL17-, IL9-secreting cluster of differentiation 4 (CD4)+ T cells. Cytometric analysis revealed no significant decrease in the percentage of Th9 cells after infliximab exposure in any of the groups, although it was lower in healthy controls than RA patients either before and after the infliximab stimulation assay. Th9 cells are IL-9-secreting T helper lymphocytes whose role in RA is still poorly known. IL-9 levels are increased in RA patients, in whom this cytokine plays a crucial role. Th9 cells are the major producers of IL-9, and their prevalence is higher in RA patients than in healthy subjects; however our experiment in vitro does not demonstrate an association between Th9 lymphocytes and the response to infliximab. Further studies are required to evaluate the real involvement of Th9 population in the immunogenicity of anti-TNF agents.
25888079 Descriptive Epidemiology of Voice Disorders in Rheumatoid Arthritis: Prevalence, Risk Fact 2016 Jan OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease which may adversely affect phonatory function. This study aimed to establish the prevalence, risks, and quality of life effects of voice disorders in RA. STUDY DESIGN: This is a cross-sectional, descriptive epidemiology study. METHODS: One hundred individuals with RA underwent a telephone interview to determine the frequency, severity, risks associated with, and quality of life burden of voice disorders. The results were analyzed using summary statistics, frequencies, chi-square tests, regression analysis, and risk ratios (P < 0.05). RESULTS: Thirty-five percent of participants with RA reported a current voice disorder which was chronic and long-standing in most cases. The prevalence of a current voice disorder did not significantly differ across age, sex, medication use, voice use patterns, medical history, or RA severity. These chronic voice disorders produced significant adverse effects on both voice-related quality of life and short form 36 health-related quality of life scales. Specific voice symptoms such as "voice-related discomfort" and "chronic throat dryness" contributed disproportionately to the quality of life burden. Of those participants with a voice disorder, only 37% had ever sought professional help to improve their voice. CONCLUSIONS: These results indicate that voice disorders are common in RA and produce significant adverse effects on quality of life. Further research is necessary to better understand the origin of these disorders and their potential response to treatment.
27311174 [Basic research overview in rheumatoid arthritis]. 2016 Jun Rheumatoid arthritis (RA) is a common autoimmune disease with a prevalence of 0.5-1.0% worldwide. Although advances in understanding the pathogenesis of RA have led to new therapeutics with good outcomes, the real cause of the disease is still unknown. RA is characterized by synovial inflammation and hyperplasia, which erodes cartilage and bone, and autoantibody production (rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)). There are many critical questions on the mechanism of the disease onset and progression: How genetic and environmental factors interact with each other? Why does the inflammatory response localize in joints? What are the key players to perpetuate synovial inflammation? In this review, we summarize pathogenetic advances in these issues especially from the point of view of basic research.
26282098 Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy. 2015 Oct 28 Notch pathway plays a pivotal role in synoviocytes involved in progression of rheumatoid arthritis (RA). Herein, we designed the Notch1 targeting siRNA delivery nanoparticles (siRNA-NPs) in order to confirm the anti-inflammatory effect in collagen-induced arthritis (CIA) model. The siRNA-NPs were successfully produced by encapsulating polymerized siRNA (poly-siRNA) into thiolated glycol chitosan (tGC) nanoparticles in aqueous condition. The in vitro Notch1 inhibition of siRNA-NPs in murine macrophage cell (RAW 264.7) was confirmed using confocal microscopy and real time PCR. Fluorescently labeled siRNA-NPs were successfully transfected in RAW 264.7 and modulated the expression of Notch1 in mRNA level. For in vivo study, siRNA-NPs exhibited the higher targeting efficiency in the arthritic joins of CIA mice, confirmed by the near-infrared fluorescence (NIRF) imaging. Furthermore, inhibition of Notch1 with siRNA-NPs resulted in retarded progression of inflammation, bone erosion, and cartilage damage in CIA mice. Novel Notch1 targeting siRNA delivery system of siRNA-NPs showed effective RA treatment by suppressing Notch1 signaling pathway without undesirable severe toxicity. Thus, Notch1 inhibiting siRNA-NPs demonstrated the great potential in RA therapeutics that was hard to be achieved using conventional drugs.
27444625 [Association between bone catabolism and anti-citrullinated protein antibodies in rheumato 2016 Oct Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis and according to the ACR-EULAR 2010 guidelines represent an important serological marker for the diagnosis of the disease. Patients with rheumatoid arthritis who are positive for ACPA display more severe bone erosion and have an overall poorer prognosis in progression of the disease compared to ACPA negative patients. For a long time it was unknown how ACPA exactly affect bone homeostasis. In this article, recent findings about the mechanisms by which ACPA contribute to bone loss are discussed.