Project description:Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Microarray analysis of 83 synovial samples provides insight into the expression-level differences between patients at the site of disease activity. Synovial samples from Rheumatoid Arthritis patients were obtained during joint resection and profiled using microarrays.
Project description:Treatment refractory Rheumatoid Arthritis (RA) is a major clinical challenge. Drug-free remission is uncommon but provides proof-of-concept that articular immune-homeostasis can be reinstated. In this project, we used single-cell RNA- to study the role of synovial tissue macrophages in maintaining disease remission. We have sequenced synovial tissue macrophages from individuals with healthy synovium (as evaluated by MRI), patients with undifferentiated arthritis (UPA), RA patients naïve to treatment, RA patients resistant to treatment and RA patients in disease remission
Project description:Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. Despite intense efforts, there isno definitive marker yet for early diagnosis RA and for monitoring the progression of this disease. We sought to catalog the proteins present in the synovial fluid of patients with rheumatoid arthritis. To identify lower abundance proteins, we undertook two approaches – we depleted the abundant proteins using a multiple affinity removal system (MARS14) column and we enriched glycoproteins using a lectin affinity column. The peptides were analyzed by LC-MS/MS on a high resolution Fourier transform mass spectrometer.
Project description:Pilot study of the feasibility and clinical significance of whole tissue and cell-type-specific transcriptional profiling of cells from synovial biopsy in Rheumatoid Arthritis (RA)
Project description:Pilot study of the feasibility and clinical significance of whole tissue and cell-type-specific transcriptional profiling of cells from synovial biopsy in Rheumatoid Arthritis (RA)
Project description:Rheumatoid arthritis (RA), a chronic and systemic disease of unknown etiology, is characterized by hyperplasia of synovial cells, which ultimately lead to the destruction of cartilage and bone. To elucidate the molecular mechanisms that lead to RA, we analyzed synovial cells established from patient with RA by oligonucleotide microarrays. Gene expression profiles reveal a novel pathophysiologic function of RA synovial cells as a generator of oxidative stress, and a self-defense mechanism against self-generated oxidative stress. Experiment Overall Design: We isolated synovial cell culture from patients with rheumatoid arthritis and osteoarthritis. Fibroblast from patient with osteoarthritis was used for the reference.
Project description:Transcriptional profiling of human rheumatoid arthritis synovial fibroblasts comparing control cells treated with BSA with cells treated with Tenascin-C.
Project description:Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Microarray analysis of 83 synovial samples provides insight into the expression-level differences between patients at the site of disease activity.
Project description:Synovial resident macrophages in humans play a key role in maintaining tissue and synovial fluid homeostasis and typically exhibit protective phenotypes. However, at the start of rheumatoid arthritis, macrophages can adopt inflammation-permissive phenotypes. The factors that influence macrophage phenotype during the early stages of arthritis are not yet fully understood. Interestingly, in mice, mechanical stress is required for the localization of joint inflammation. Given the critical roles of macrophages, we investigated whether mechanosensation contributes to the regulation of macrophage phenotypes. PIEZO1, a well-established mechanosensor expressed on macrophages, regulates various macrophage functions, including migration and phagocytosis. We found that PIEZO1 activation in macrophages shifted their phenotype to a tissue-resident (MERTKhigh, CD36high), inflammation-permissive phenocopy (TREM2low, VSIG4low), with elevated MHC class II and cytokine secretion. Additionally, in vivo activation of PIEZO1 in mice produced similar effects in synovial tissue macrophages (STMs) and led to increased recruitment of monocytes and neutrophils. By dissecting the PIEZO1 signalling pathway, we were able to restore the protective macrophage phenotype by inhibiting calpain signalling and knocking-out HIF1α, both downstream mediators of PIEZO1 activation. Furthermore, we observed that PIEZO1 expression is present in synovial macrophages from patients with active rheumatoid arthritis and decreases during remission, suggesting a link between macrophage PIEZO1 expression and disease activity