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Arthritis & Rheumatology

Akihiko Hasegawa, Tomo Yonezawa, Noboru Taniguchi, Koji Otabe, Yukio Akasaki, Tetsuya Matsukawa, Masahiko Saito, Masashi Neo, Lihua Y Marmorstein, Martin K Lotz
OBJECTIVES: The EFEMP1 gene encoding fibulin-3 is specifically expressed in the superficial zone of articular cartilage. This study examined fibulin-3 expression patterns in joint aging and osteoarthritis (OA) and the role of fibulin-3 in OA pathogenesis. METHODS: Immunohistochemical analysis was performed on normal and OA human and mouse knee cartilage. Experimental OA was induced in wild type and fibulin-3(-/-) mice and OA severity was evaluated by histological scoring...
October 25, 2016: Arthritis & Rheumatology
Smriti K Raychaudhuri, Christine Abria, Siba P Raychaudhuri
No abstract text is available yet for this article.
October 21, 2016: Arthritis & Rheumatology
Heba M Ismail, Athanasios Didangelos, Tonia L Vincent, Jeremy Saklatvala
Objectives Mechanical injury to cartilage predisposes to osteoarthritis (OA). Wounding the articular cartilage surface causes rapid activation of MAP kinases and NFκB mimicking the response to inflammatory cytokines. Here, we identify the upstream signalling mechanisms involved. Methods Cartilage was injured by dissecting it from the articular surface of porcine metacarpophalangeal joints (MCP) or by avulsing murine proximal femoral epiphyses. Protein phosphorylation was assayed by Western blotting of cartilage lysates...
October 21, 2016: Arthritis & Rheumatology
Alexis Ogdie, William J Taylor, Tuhina Neogi, Jaap Fransen, Tim L Jansen, H Ralph Schumacher, Worawit Louthrenoo, Janitzia Vazquez-Mellado, Maxim Eliseev, Geraldine McCarthy, Lisa K Stamp, Fernando Perez-Ruiz, Francisca Sivera, Hang-Korng Ea, Martijn Gerritsen, Giovanni Cagnotto, Lorenzo Cavagna, Chingtsai Lin, Yin-Yi Chou, Anne-Kathrin Tausche, Manuella Lima Gomes Ochtrop, Matthijs Janssen, Jiunn-Horng Chen, Ole Slot, Juris Lazovskis, Douglas White, Marco A Cimmino, Till Uhlig, Nicola Dalbeth
OBJECTIVES: To examine the performance of ultrasound for the diagnosis of gout using presence of monosodium urate (MSU) crystals as the gold standard. METHODS: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multi-center observational cross-sectional study of consecutive subjects with at least one swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with MSU crystal confirmation...
October 16, 2016: Arthritis & Rheumatology
A J Kivitz, S R Gutierrez-Ureña, J Poiley, M C Genovese, R Kristy, K Shay, X Wang, J P Garg, A Zubrzycka-Sienkiewicz
OBJECTIVE: To evaluate efficacy and safety of orally administered once-daily peficitinib in combination with methotrexate (MTX) in patients with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response to MTX. METHODS: In this multinational, phase IIb, randomized, double-blind, placebo-controlled, dose-ranging trial, patients with RA (N=378) were treated with peficitinib 25 mg, 50 mg, 100 mg, 150 mg + MTX, or matching placebo + MTX once daily for 12 weeks (NCT01554696)...
October 16, 2016: Arthritis & Rheumatology
José Antonio Bernal, Mariano Andrés, María Fernanda Palmero
No abstract text is available yet for this article.
October 16, 2016: Arthritis & Rheumatology
Eugene Y Kissin, Michael H Pillinger
No abstract text is available yet for this article.
October 16, 2016: Arthritis & Rheumatology
Lindsay E Nyhoff, Leslie J Crofford, Peggy L Kendall
No abstract text is available yet for this article.
October 16, 2016: Arthritis & Rheumatology
Panna Sanga, Nathaniel Katz, Elena Polverejan, Steven Wang, Kathleen M Kelly, Juergen Haeussler, John Thipphawong
OBJECTIVE: To evaluate long-term safety and efficacy of fulranumab in patients with moderate-to-severe chronic osteoarthritis (OA) knee or hip pain. METHODS: In this placebo-controlled, phase-2 double-blind (DB) extension study, patients who were equally randomized to 1mgQ4wk, 3mgQ8wk, 3mgQ4wk, 6mgQ8wk, or10mgQ8wk fulranumab (s.c.) or placebo in the 12-week DB efficacy phase, and completed this DB efficacy phase, were eligible to continue the dose throughout a 92-week extension phase followed by a 24-week posttreatment follow-up (PFTU)...
October 16, 2016: Arthritis & Rheumatology
Hal M Hoffman, Lori Broderick
No abstract text is available yet for this article.
October 16, 2016: Arthritis & Rheumatology
Rebecca Baum, Shruti Sharma, Jason M Organ, Christopher Jakobs, Veit Hornung, David B Burr, Ann Marshak-Rothstein, Katherine A Fitzgerald, Ellen M Gravallese
OBJECTIVE: Cytosolic DNA sensors detect microbial DNA and promote type I interferon and pro-inflammatory cytokine production through the adaptor stimulator of interferon genes (STING) to resolve infection. Endogenous DNA also engages the STING pathway, contributing to autoimmune disease. We identified a novel role for STING in bone in arthritic DNase II/IFNaR double deficient (DKO) mice, and sought to define the bone phenotype in these mice and to address mechanism. METHODS: Bone parameters were evaluated in DKO, STING/DNaseII/IFNaR triple deficient and control mice by microcomputed tomography and histomorphometry...
October 14, 2016: Arthritis & Rheumatology
Brooke Rhead, Calliope Holingue, Michael Cole, Xiaorong Shao, Hong L Quach, Diana Quach, Khooshbu Shah, Elizabeth Sinclair, John Graf, Thomas Link, Ruby Harrison, Elior Rahmani, Eran Halperin, Wei Wang, Gary S Firestein, Lisa F Barcellos, Lindsey A Criswell
Objectives Our study aimed to determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients were also differentially methylated in peripheral blood samples. Methods We measured 371 genome-wide DNA methylation profiles from 63 RA cases and 31 controls, in CD14+ monocytes, CD19+ B cells, CD4+ memory T cells and CD4+ naïve T cells, using Illumina HumanMethylation450 (450k) BeadChips. Results We found that of 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naïve T cells of RA cases compared to controls...
October 9, 2016: Arthritis & Rheumatology
Robert W Hoffman, Joan T Merrill, Marta M E Alarcón-Riquelme, Michelle Petri, Ernst R Dow, Eric Nantz, Laura K Nisenbaum, Krista M Schroeder, Wendy J Komocsar, Narayanan B Perumal, Matthew D Linnik, David C Airey, Yushi Liu, Guilherme V Rocha, Richard E Higgs
OBJECTIVE: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. METHODS: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors...
October 9, 2016: Arthritis & Rheumatology
Rodger Stitt, Jess D Edison, Christopher Tracy
No abstract text is available yet for this article.
October 9, 2016: Arthritis & Rheumatology
Roy Fleischmann, Michael Schiff, Désirée van der Heijde, Cesar Ramos-Remus, Alberto Spindler, Marina Stanislav, Cristiano A F Zerbini, Sirel Gurbuz, Christina Dickson, Stephanie de Bono, Douglas Schlichting, Scott Beattie, Wen-Ling Kuo, Terence Rooney, William Macias, Tsutomu Takeuchi
Objective This Phase 3 study evaluated baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, as monotherapy or combined with methotrexate (MTX) compared to MTX in patients with active rheumatoid arthritis (RA) with no or minimal prior conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and naive to biologic DMARDs. Methods Patients (N=588) were randomized 4:3:4 (MTX: baricitinib 4 mg once daily: baricitinib 4 mg + MTX) for 52 weeks. The primary endpoint assessment was noninferiority of baricitinib monotherapy to MTX based on American College of Rheumatology 20% (ACR20) response at Week 24...
October 9, 2016: Arthritis & Rheumatology
David B Guiliano, Helen North, Eleni Panayoitou, Elaine C Campbell, Kirsty McHugh, Fiona G M Cooke, Marine Silvestre, Paul Bowness, Simon J Powis, Antony N Antoniou
Objective - HLA-B27 is associated with the inflammatory spondyloarthropathies (SpAs). Of significance, subtypes HLA-B*27:06 and HLA-B*27:09 are not associated with the SpAs. These subtypes primarily differ from the HLA-B*27:05 disease associated allele at residues 114 and 116 of the heavy chain, part of the F pocket of the antigen-binding groove. Dimerisation of HLA-B27 during assembly has been implicated in disease onset. This study investigated the factors influencing differences in dimerisation between disease associated and non-associated HLA-B27 alleles...
October 9, 2016: Arthritis & Rheumatology
Olga Katsara, Mukundan Attur, Rachel Ruoff, Steven B Abramson, Victoria Kolupaeva
Objectives Degeneration of articular cartilage is central to OA pathology; however, the molecular mechanisms leading to these irreversible changes are still poorly understood. Here, we investigated how changes in the chondrocyte translational apparatus may contribute to the pathology of OA. Methods Normal and OA human knee cartilage was used to analyze the activity of different components of the translational machinery. Chondrocytes isolated from lesional and non-lesional areas of OA cartilage were used to estimate relative rate of protein synthesis by metabolic labeling...
October 1, 2016: Arthritis & Rheumatology
Iván Ferraz-Amaro, Robert Winchester, Peter K Gregersen, Richard J Reynolds, Mary Chester Wasko, Anette Oeser, Cecilia P Chung, C Michael Stein, Jon T Giles, Joan M Bathon
OBJECTIVE: Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single nucleotide polymorphisms (SNPs). Since CAD is increased in rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs are increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD. METHODS: CAD was assessed by coronary artery calcification (CAC) using computed-tomography in 561 patients with RA...
October 1, 2016: Arthritis & Rheumatology
Edward M Behrens
No abstract text is available yet for this article.
October 1, 2016: Arthritis & Rheumatology
Magdalena Janina Laskaj, Anne Troldborg, Ellen-Margrethe Hauge, Shervin Bahrami, Kristian Stengaard-Pedersen
OBJECTIVES: Human Endogenous Retroviruses (HERVs) are remnants of past retroviral infections in the human genome and have been implicated in different aspects of human biology. The aim of this study was to identify HERVs which are associated with the pathogenesis of Rheumatoid diseases represented by Systemic Lupus Erythematosus (SLE). METHODS: The study subjects included 45 female patients with SLE and 50 geographically and age matched healthy. Real-time RT-PCR analysis was used to examine the transcription levels of 11 genes with coding capacity for complete envelope protein in these individuals...
October 1, 2016: Arthritis & Rheumatology
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