miR-17-5p reduces inflammation and bone erosions in collagen induced arthritis mice and directly targets the JAK-STAT pathway in rheumatoid arthritis fibroblast-like synoviocytes
Objective: Our objective was to study miR expression in rheumatoid arthritis (RA) phenotype, along with the effects and mechanism of action of miR-17-5p.
Methods: An array mir done in synovial tissue biopsy of n = 3 naive erosive and non-erosive RA patients. miR-17 lipoplex delivered intra-articularly in a murine model of collagen-induced arthritis. Clinical, histological and structural effects studied for arthritis. In-depth study of miR-17 mechanism-of-action is carried out in SD RA-FLS isolated from synovial tissue.
Results: 55 miRNAs including miR-17 reduced in erosive RA. miR-17 transfection at the foot of clinical rheumatoid reduces inflammation from day 2 to 7 (score 2.8 vs 1.9, p = 0.03). synovial B cells, T cells, macrophages and polynuclear neutrophils infiltrate was significantly reduced. structural damage also decreased as shown by the decrease in the number of osteoclasts (TRAP surface / total surface of 32 vs 18%, p = 0.005) and a score of erosion with the analysis of CT (score 2.9 vs. 1.7, p = 0.023). pro-inflammatory cytokines IL-6 family, and the expression of IL-1β was also reduced significantly, but not TNF. miR17 directly targeting the 3′-translated region of STAT3 and JAK1. STAT3 and JAK1 mRNA and protein expression was reduced in RA-FLS follows miR-17 transfection. STAT3 and JAK1 mRNA and activation of STAT3 assessed by immunohistochemistry was also reduced in the foot injected (% area stained 93 vs 62, p = 0.035).
Conclusions: We demonstrate the role of anti-inflammatory and anti-erosive of miR-17 in vivo. This effect involves the suppression of IL-6 autocrine loop strengthen families through direct targeting JAK1 and STAT3.
miR-17-5p reduces inflammation and bone erosions in collagen induced arthritis mice and directly targets the JAK-STAT pathway in rheumatoid arthritis fibroblast-like synoviocytes
The emerging role of fibroblast-like synoviocytes-mediated synovitis in osteoarthritis: Updates
Osteoarthritis (OA), a degenerative disease of the most ubiquitous affecting all the joints, characterized by cartilage degradation and synovial inflammation. Although the pathogenesis of OA is still poorly understood, synovial inflammation is known to play an important role in the development of OA. However, studies in OA pathophysiology have focused more on the degeneration of cartilage and osteophytes and not in the synovium is inflamed and thickened.
Fibroblast like synoviocytes (FLS) produces a series of pro-inflammatory regulator, such as inflammatory cytokines, nitric oxide (NO) and prostaglandin E2 (PGE2). The regulator is positively associated with clinical symptoms of OA, such as inflammatory pain, joint swelling and disease progression. A better understanding of the inflammatory immune response in OA-FLS could provide a new approach for a comprehensive strategy for the treatment of OA.
Here, we have summarized the literature recently published referring to the epigenetic modification, activated signaling pathways and related inflammatory factors involved in inflammation-mediated OA-FLS. In addition, clinical trials related to current and future perspectives are also summarized.
Description: Human synoviocytes (HS), the predominant cell type of healthy synovial tissue, are fibroblast-like cells. The Synoviocytes form a distinct structure called the synovial lining layer. Electron microscopy revealed extensive cell-to-cell contacts within the lining layer. The Synoviocytes produce synovial fluid components and are responsible for absorption from the joint cavity, and for blood/synovial fluid exchanges. The synoviocytes proliferate, show anchorage-independent growth, and also secrete a variety of effector molecules that promote inflammation and joint destruction and, themselves are part of a complex network of autocrine and paracrine acting factors. The synoviocytes express cadherin-11 providing new insight into synovial tissue organization and morphogenesis and of interest as a therapeutic target.HS from Gentaur Research Laboratories are isolated from human synovium. HS are cryopreserved at passage one cultures and delivered frozen. Each vial contains 5×10^5 cells in 1 ml volume. HS are characterized by their fibroblast-like morphology, growth pattern and immunocytochemistry of CD 90 and fibronectin. HS are negative for HIV-1, HBV, HCV, mycoplasma, bacteria, yeast and fungi. HS are guaranteed for 15 population doublings at the conditions provided by Gentaur Research Laboratories.
Description: Human Fibroblast-Like Synoviocytes (HFLS) are isolated from normal synovial tissues. They are cryopreserved at second passage and can be cultured and propagated at least 5 population doublings.
Renal Cancer Associated Fibroblasts, 1,000,000 Cells, cryopreserved
Description: Human Fibroblast-Like Synoviocytes (HFLS) are isolated from synovial tissues obtained from patients with Rheumatoid Arthritis (RA) / Osteoarthritis (OA). They are cryopreserved at second passage and can be cultured and propagated at least 5 population doubling.
Synoviocyte Growth Medium, Ready-to-Use, 500 ml, 10% Human Serum Supplement
Description: Human Fibroblast-Like Synoviocytes (HFLS) are isolated from synovial tissues obtained from patients with Rheumatoid Arthritis (RA) / Osteoarthritis (OA). They are cryopreserved at second passage and can be cultured and propagated at least 5 population doubling.
COOLCELL SV2 STEMCELL CRYOPRESERVATION SYSTEM INCLUDES THE XT STARTER BENCHTOP COOLER, COOLRACK SV2 AND COOLCELL SV2 CELL FREEZING CONTAINER FOR 12 INJECTABLE VIALS
COOLCELL SV10 STEMCELL CRYOPRESERVATION SYSTEM INCLUDES THE XT STARTER BENCHTOP COOLER, COOLRACK SV10 AND COOLCELL SV10 CELL FREEZING CONTAINER FOR 6 INJECTABLE VIALS
Description: The human tissue blot is designed for proteomics research in screening for antibody and protein expression. It carries 9 different human normal tissue lysates with 15 µg of total cellular protein in each lane. Proteins were separated in 4-20% SDS-PAGE gel and transferred onto nitrocellulose membrane. The human normal tissues included in the blot are brain, heart, kidney, liver, lung, pancreas, skeletal muscle, skin, and spleen.
Description: The human tissue blot is designed for proteomics research in screening for antibody and protein expression. It carries 9 different human normal tissue lysates with 15 µg of total cellular protein in each lane. Proteins were separated in 4-20% SDS-PAGE gel and transferred onto nitrocellulose membrane.The human normal tissues included in the blot are left cerebellum, right cerebellum, frontal lobe, occipital lobe, parietal lobe, whole eye, spinal cord, temporal lobe, and thalamus.
Collecting evidence suggests that miR-483-3p involved in maintaining the biological properties of human cancers. However, the biological role in rheumatoid arthritis (RA) remains unknown. levels of miR-483-3p in synovial tissue samples and fibroblast-like synoviocytes (FLSs) is determined by using quantitative real-time PCR. The CCK-8 assay and Edu staining was performed to assess cell proliferation in RA FLSs after transfection with miR-483-3p mimics or inhibitors. Flow cytometry with Annexin V-FITC staining or PI staining was performed to assess apoptosis or cell cycle progress in FLSs RA, respectively.
Shelby
