- Small RNAs detected in exosomes derived from the MH7A synovial fibroblast cell line with TNF-α stimulation. [Journal Article]
- PlosPLoS One 2018; 13(8):e0201851
- Rheumatoid arthritis (RA) is an autoimmune disease that causes the chronic inflammation of the joints. Intercellular communication containing synovial fibroblasts seems to play a major role in RA pat...
Rheumatoid arthritis (RA) is an autoimmune disease that causes the chronic inflammation of the joints. Intercellular communication containing synovial fibroblasts seems to play a major role in RA pathogenesis. In this study, to better understand intercellular communication related to RA pathogenesis, we identified exosomal microRNAs (miRNAs) derived from synovial fibroblasts. Exosomes were collected from an RA synovial fibroblast (RASF) cell line, namely, MH7A, with or without stimulation by tumor necrosis factor alpha (TNF-α). We used small RNA sequencing to analyze the profile of small RNAs, including miRNAs, in MH7A exosomes and cells. By using differential expression analysis, we identified four miRNAs (miR-155-5p, miR-146a-5p, miR-323a-5p, and miR-1307-3p) that are upregulated in exosomes with TNF-α stimulation. The identification of miR-155-5p and miR-146a-5p which have been reported in RA patients demonstrated the validity of our experimental model. Other two miRNAs were newly identified. miR-323a-5p was predicted to target the protein encoding gene CD6, which attenuates T-cell activation signals, and miR-1307-3p was predicted to target the protein encoding gene N-myc downstream-regulated gene 2 (NDRG2), which inhibits osteoclast-related gene expression. The results suggested that these miRNAs might be involved in RA pathogenesis. We hope our results will help us understand the role of RASF exosomes in RA pathogenesis.
- Peptide-directed liposomal delivery improves the therapeutic index of an immunomodulatory cytokine in controlling autoimmune arthritis. [Journal Article]
- JCJ Control Release 2018 Aug 04; 286:279-288
- Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial tissue of the joints. Inadequately controlled disease may cause severe joint damage and deform...
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial tissue of the joints. Inadequately controlled disease may cause severe joint damage and deformity. Currently, the anti-arthritic drugs are given systemically, and therefore, they are widely distributed to other organs that are not the intended therapeutic targets. Accordingly, using a particular dose/regimen of a drug to achieve an effective local concentration of the drug in arthritic joints may lead to expected adverse effects involving other organs. Thus, improved methods of drug delivery are needed for arthritis therapy. One attractive approach is the targeting of a systemically administered drug to the inflamed joints. We describe here a prototypic drug delivery system using a novel peptide ligand denoted as ART-1. We previously reported ART-1 (=ADK) as a peptide that preferentially homes to the inflamed joints of arthritic rats and binds to synovial endothelial cells. We tested the ART-1-coated liposomes encapsulating a fluorescent compound for binding to activated endothelial cells in vitro and homing to arthritic joints in vivo, compared to control liposomes lacking the ART-1 coating. Similar liposomes but encapsulating an immunomodulatory cytokine interleukin-27 (ART-1-IL-27 liposomes) were tested for their anti-arthritic activity compared with control liposomes. ART-1-displaying liposomes showed better binding to endothelial cells as well as in vivo homing to arthritic joints compared to control liposomes. Furthermore, ART-1-IL-27 liposomes, when intravenously injected to arthritic rats after the onset of arthritis, were more effective in suppressing disease progression than control-IL-27 liposomes lacking ART-1 or free IL-27 at an equivalent dose of IL-27. In addition, ART-1-directed liposomal IL-27 had a better safety profile than undirected liposomal IL-27 or free IL-27, thereby offering an improved therapeutic index for IL-27 therapy. These results provide a proof-of concept for the use of a novel joint-homing peptide for targeted delivery of drugs including biologics or small molecule compounds to arthritic joints with enhanced efficacy and reduced systemic exposure. This targeted therapy platform may be suitable for use in RA patients.
- The effect of caveolin-1 knockdown on interleukin-1β-induced chemokine (C-C motif) ligand 2 expression in synovial fluid-derived fibroblast-like synoviocytes from patients with rheumatoid arthritis. [Journal Article]
- ACAdv Clin Exp Med 2018 Aug 06
- CONCLUSIONS: Our study demonstrates that CCL2 expression in sfd-FLSs is CAV1-dependent, but only at transcript level. As the function of CAV1 has not been unequivocally determined, more studies are needed to confirm the role of CAV1 in inflammatory processes related to RA.
- Four Methods of Recruiting Couples Into a Longitudinal Study of Physical Activity in People With Osteoarthritis: Recruitment, Retention, and Lessons Learned. [Journal Article]
- FPFront Public Health 2018; 6:197
- Increases in physical activity can reduce joint pain among people with osteoarthritis (PWOA) who are insufficiently physically active. Because evidence suggests that social support from intimate part...
Increases in physical activity can reduce joint pain among people with osteoarthritis (PWOA) who are insufficiently physically active. Because evidence suggests that social support from intimate partners may help PWOA become more active, researchers have been interested in recruiting couples to studies of physical activity interventions; however, little guidance exists describing efficient and effective strategies for engaging couples in research. We describe methods used to recruit couples and contrast methods in terms of the proportion of individuals enrolled, sample demographic composition, retention, and resources. We used four recruitment methods to enroll couples in a longitudinal study of PWOA: (1) visiting community sites, (2) sending university-wide emails, (3) contacting patients identified through electronic medical records (EMR), and (4) partnering with a county-based osteoarthritis (OA) research cohort. We found that these methods differed in their challenges and contribution to enrollment goals but demonstrated similar levels of retention. We contacted 747 PWOA; 56% were screened for eligibility and 23% enrolled in the study. The largest proportion of participants recruited were from the email method (35.1%), followed by the community (26%), EMR (22.0%), and OA cohort (19.6%). Couples enrolled through the different methods differed by age, employment, education, and household income. Across the methods for both PWOA and partners, over 80% of participants were non-Hispanic white, about 11% were non-Hispanic black, and 6-8% identified as another race. Over 12 months of follow-up, 31 (17.9%) PWOA and 36 (20.8%) partners were lost to follow-up. Using four distinct recruitment methods allowed us to meet recruitment goals and provided a broader, more diverse population compared to using one method. We recommend that researchers consider several recruitment methods to meet enrollment goals, to ensure a diverse sample, and to match available resources. The lessons learned from this research fill a critical gap in the understanding of how to overcome barriers to recruiting and retaining couples in behavioral research.
- Outcome of Allogeneic Adult Stem Cell Therapy in Dogs Suffering from Osteoarthritis and Other Joint Defects. [Journal Article]
- SCStem Cells Int 2018; 2018:7309201
- Osteoarthritis is a common condition that causes joint pain and stiffness that affects both humans and dogs. In Australia, allogeneic canine adipose-derived mesenchymal stem cells for therapy have be...
Osteoarthritis is a common condition that causes joint pain and stiffness that affects both humans and dogs. In Australia, allogeneic canine adipose-derived mesenchymal stem cells for therapy have been commercially available since 2010. In this report, we describe the outcome of the treatment of two hundred and three dogs diagnosed with degenerative arthritis with severe chronic pain in joints causing lameness at walk, reduced mobility, and functional disability. Posttreatment assessment data after 10 weeks revealed significant improvement (p < 0.007) of the symptoms: pain reduction, improvement of mobility, and increased daily activity as measured as quality of life score. Ninety percent of young dogs (<9 years) showed excellent improvement in pain and mobility and were able to run and resume normal activity. Sixty percent of older dogs showed good improvement. However, 12% of dogs did not exhibit any change in symptoms; one dog showed worsening of the symptoms. This report provides the support for the safety and efficacies of allogeneic adipose-derived mesenchymal stem cells in a regenerative therapeutic veterinary model.
- Rheumatoid arthritis-like features in Hansen disease: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(29):e11590
- CONCLUSIONS: The correct diagnosis of Hansen disease involving joints depends on the combination of medical history, careful physical examination, and laboratory examination.
- The frequency of Chronic Joint Pain Following Chikungunya Virus Infection A Colombian Cohort Study comment on the article by Chang et al. [Letter]
- ARArthritis Rheumatol 2018 Jul 17
- Chang et al. need to be congratulated to show that Chikungunya (CHIK) is a public health issue that is not only limited to Asia and Africa but even a threat in the Americas. It is emerging as a globa...
Chang et al. need to be congratulated to show that Chikungunya (CHIK) is a public health issue that is not only limited to Asia and Africa but even a threat in the Americas. It is emerging as a global pandemic. We had 366 CHIK positive cases reported in and around Chandigarh from September 2016 to January 2017 as per the records of National Vector Disease Control Programme. We share our experience of 99 serologically confirmed cases of CHIK patients by NIV Chikungunya IgM Capture ELISA Kit, followed up for one year. This article is protected by copyright. All rights reserved.
- Chikungunya on kidney transplant recipients: Is it the same? [Journal Article]
- TTransplantation 2018 Jul 13
- CONCLUSIONS: The chance of CHIKV infection becoming chronic arthralgia in KTR was not different from data in literature. Seven patients presented AKI in the acute phase of infection, although that did not persist. Previous costicosteroids use did not relate with AKI or chronic arthralgia.
- Foot function in rheumatoid arthritis patients: a cross-sectional study. [Journal Article]
- CRClin Rheumatol 2018 Jul 14
- Rheumatoid arthritis (RA) is a chronic disease that affects mainly small joints from hands and feet. The aims of this study were to analyze the prevalence of foot involvement in a sample of Brazilian...
Rheumatoid arthritis (RA) is a chronic disease that affects mainly small joints from hands and feet. The aims of this study were to analyze the prevalence of foot involvement in a sample of Brazilian RA patients and to explore the influence of disease variables such as inflammatory activity, serological, and epidemiological profile in this type of involvement. One hundred RA patients and 100 healthy controls paired for gender, age, and body mass index answered the FFI-BR (Foot Functional Index-Brazilian version) that evaluates foot function. RA patients had epidemiological and clinical data collection upon direct questioning and chart review. C-reactive protein (CRP), ESR (erythrocyte sedimentation rate), and DAS28-ESR were used to measure disease activity. In the RA sample, 98% had foot pain versus 76% in the controls (p < 0.0001; OR = 15.4; 95% CI = 3.4-67.5); 96% had some difficulty in function versus 66% of controls (p < 0.0001; OR = 12.3; 95% CI = 4.1-36.5); and 73% had some incapacity versus 20% of controls (p < 0.0001; OR = 10.8; 95% CI = 5.5-20.9). Values of FFI-BR showed correlation with ESR (p = 0.006), CRP (p = 0.01), and DAS28-ESR (p < 0.0001). No association between FFI-BR total score and gender, ethnic background, positive rheumatoid factor, tobacco exposure, and any of used medications was found (all p = ns). The majority of RA patients suffers from foot problems and was associated with inflammatory biomarkers. The control of inflammatory activity may help in the treatment of this problem.
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- Reply to Comments on "The frequency of Chronic Joint Pain Following Chikungunya Virus Infection A Colombian Cohort Study". [Journal Article]
- ARArthritis Rheumatol 2018 Jul 12
- We thank Sharma et al. and Cardona-Ospina et al. for sharing their experience and discussion. One of the limitations of our evaluation of the cohort was that we have not yet determined the incidence ...
We thank Sharma et al. and Cardona-Ospina et al. for sharing their experience and discussion. One of the limitations of our evaluation of the cohort was that we have not yet determined the incidence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in all 485 patients. This will be a valuable assessment to perform. However, RF and anti-CCP antibodies were measured in a subset of chikungunya arthritis patients1 and no CHIKV arthritis patients had elevated anti-CCP antibodies, 9% had IgM-RF antibodies, and 12% had IgG-RF antibodies. This article is protected by copyright. All rights reserved.