Enabled fibroblast-like synoviocytes (FLSs) plays a central role in synovial pannus formation and joint destruction in rheumatoid arthritis (RA). FLSs targeting could be a potential therapeutic strategy. The purpose of this study was to explore the role of c-Jun N-terminal kinase (JNK) in the proliferation, migration and invasion FLSs hedeghog promoted by Sonic (SHH) signaling pathway in patients with RA. SHH signaling activation was evaluated by real-time PCR and Western Blot.
The level of phosphorylation of JNK and c-Jun was detected by Western Blot. FLSs proliferation was quantified by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Cell migration and invasion was assessed by wound healing assay and Transwell chamber assay. Invasion of FLSs in vivo was evaluated using humane animal synovitis models. We observed that treatment SHH agonist (SAG) significantly increased the level of phosphorylation of JNK and c-jun, while SHH antagonist (cyclopamine) significantly decreased the expression of phospho-JNK and phospho-c-Jun in FLSs. Elevated level of phospho-c-Jun is stimulated by SAG decreased in the presence of JNK inhibitor (SP600125) (P <0.001).
FLSs proliferation, migration and invasion promoted by SHH agonist (P <0.05). However, enhanced aggressiveness FLSs abolished in the presence of JNK inhibitor (P <0.05). In vivo studies show that FLSs invasion into cartilage increased by SHH excess and excessive invasive inhibited by blockade of JNK signaling (P <0.01). These results indicate that JNK is one molecule downstream of SHH signaling in mediating the effects of FLSs. These findings indicate that SHH-JNK signaling may be a potential therapeutic target to suppress aggressiveness FLSs and prevent articular damage of RA.
Sonic Hedgehog Regulates Proliferation, Migration and Invasion of Synoviocytes in Rheumatoid Arthritis via JNK Signaling
Hsa_circ_0088036 promotes proliferation and migration of fibroblast-like synoviocytes by rubbing miR-140-3p and upregulating SIRT 1 expression in rheumatoid arthritis
Circular RNAs (circRNAs) has been shown to play an important role in the development and progression of various cancers by serving as microRNA sponges to regulate the expression of target genes. Although circRNAs depth studies have been carried out, functional and pathological significance in autoimmune diseases, including rheumatoid arthritis (RA), is still unclear.
Our previous studies verified that hsa_circ_0088036 (circ0088036) was significantly increased in peripheral blood mononuclear cells of patients with RA. This study aims to explore circ0088036 role in the pathogenesis of RA. The circ0088036 / miR-140-3p / silent information regulator 1 (SIRT 1) axis predicted by bioinformatics tools. Circ0088036 found to aberrantly upregulated in fibroblast-like synoviocytes (FLSs) in RA compared with FLSs in osteoarthritis (OA).
Functionally, regulated circ0088036 promoted proliferation and migration from RA-FLSs. Mechanically, circ0088036 miR-140-3p act as a sponge to upregulate the expression of SIRT 1, and then promote the development of RA. In conclusion, this study revealed that circ0088036 may play an important role in promoting the pathogenesis of synovial through circ0088036 / miR-140-3p / SIRT 1 axis in RA, provides new insight into circRNAs for RA progression.Fibroblast-like synoviocytes (FLS) is a cell co-promoting layer rheumatoid arthritis (RA) pathology.
Human Fibroblast-Like Synoviocyte Normal Tissue, Adult
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.
Human Fibroblast-Like Synoviocyte Osteo Arthritis, Adult
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.
Human Fibroblast-Like Synoviocyte Rheumatoid Arthritis, Adult
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.
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: Cell Type iPSCPrimary Tissue Activated fibroblast from primary keratocytesReprogramming Method Episomal PlasmidDisease Keratoconus; Cells are only guaranteed with purchase of Gentaur Media and Gentaur Extra Cellular Matrix for appropriate cell culture, for 30 days from the date of shipment.
Description: A Rabbit polyclonal antibody against Mouse Fibroblast Growth Factor Receptor Like Protein 1 (FGFRL1). This antibody is labeled with APC-Cy7.
Description: A Rabbit polyclonal antibody against Mouse Fibroblast Growth Factor Receptor Like Protein 1 (FGFRL1). This antibody is labeled with Biotin.
Description: Recombinant mouse bFGF is a disulfide-linked homodimeric protein consisting of 146 amino acid residue subunits, and migrates as an approximately 16 kDa protein under non-reducing and reducing conditions in SDS-PAGE. Optimized DNA sequence encoding Mouse basic Fibroblast Growth Factor mature chain was expressed in E. coli.
Description: Recombinant mouse bFGF is a disulfide-linked homodimeric protein consisting of 146 amino acid residue subunits, and migrates as an approximately 16 kDa protein under non-reducing and reducing conditions in SDS-PAGE. Optimized DNA sequence encoding Mouse basic Fibroblast Growth Factor mature chain was expressed in E. coli.
Mouse Bladder PrimaCell™2: Normal Bladder Fibroblasts
Description: Recombinant murine aFGF (acidic Fibroblast Growth Factor) is a disulfide-linked monomer protein consisting of 141 a.a. and migrates as an approximately 16 kDa protein under reducing and non-reducing conditions. Native murine aFGF, generated by the proteolytic removal of the signal peptide and propeptide, has a calculated mass of 16 kDa. Optimized DNA sequence encoding murine acidic Fibroblast Growth Factor mature chain was expressed in E. coli.
Description: Recombinant murine aFGF (acidic Fibroblast Growth Factor) is a disulfide-linked monomer protein consisting of 141 a.a. and migrates as an approximately 16 kDa protein under reducing and non-reducing conditions. Native murine aFGF, generated by the proteolytic removal of the signal peptide and propeptide, has a calculated mass of 16 kDa. Optimized DNA sequence encoding murine acidic Fibroblast Growth Factor mature chain was expressed in E. coli.
Description: A competitive ELISA for quantitative measurement of Mouse Fibroblast surface protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Fibroblast surface protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Fibroblast surface protein in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Disease-modifying antirheumatic agents today (DMARDs) operates through systemic immunosuppression. FLS-targeted approach can potentially be combined with DMARDs for RA improve control without increasing immunosuppression. Here, we assess the potential of the immunoglobulin-like domains 1 and 2 (IG1 & 2), which activates the protein bait sigma receptor tyrosine phosphatases (PTPRS) on FLS, for the treatment of RA.
Shelby
