Regulation of fibroblast-like synoviocyte transformation by transcription factors in arthritic diseases

Bhattaram, Pallavi; Jones, Kyle M.

doi:10.1016/j.bcp.2019.03.018

Cited by 17 publications

(11 citation statements)

References 102 publications

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“…In RA, diffuse synovial inflammation is observed, while synovitis in OA is usually in patchy distribution, confined to sites adjacent to cartilage damage 30. The increased migratory and invasive ability of FLS have been more extensively recognized in RA than in OA 9,32, and several transcription factors are reported to be potentially responsible for the FLS transformation in inflammatory arthritic diseases 33,34. In OA, several studies suggested that activation of receptors for advanced glycation end products and up-regulated expression of chemokine receptor 3 and cadherin-11 could increase the catabolic activity and migratory/invasive capacity of FLS 35-37.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches

Chen

Chang

et al. 2019

Int. J. Med. Sci.

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Synovitis in osteoarthritis (OA) the consequence of low grade inflammatory process caused by cartilage breakdown products that stimulated the production of pro-inflammatory mediators by fibroblast-like synoviocytes (FLS). FLS participate in joint homeostasis and low grade inflammation in the joint microenvironment triggers FLS transformation. In the current study, we aimed to identify differentially expressed genes and potential miRNA regulations in human OA FLS through deep sequencing and bioinformatics approaches. The 245 differentially expressed genes in OA FLS were identified, and pathway analysis using various bioinformatics databases indicated their enrichment in functions related to altered extracellular matrix organization, cell adhesion and cellular movement. Moreover, among the 14 dysregulated genes with potential miRNA regulations identified, src kinase associated phosphoprotein 2 (SKAP2), adaptor related protein complex 1 sigma 2 subunit (AP1S2), PHD finger protein 21A (PHF21A), lipoma preferred partner (LPP), and transcription factor AP-2 alpha (TFAP2A) showed similar expression patterns in OA FLS and OA synovial tissue datasets in Gene Expression Omnibus database. Ingenuity Pathway Analysis identified the dysregulated LPP participated in cell migration and cell spreading of OA FLS, which was potentially regulated by miR-141-3p. The current findings suggested new perspectives into understanding the novel molecular signatures of FLS involved in the pathogenesis of OA, which may be potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches

Chen

Chang

et al. 2019

Int. J. Med. Sci.

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“…RA FLSs display cancerous properties in inflamed synovial tissue, whereby they exhibit local tumor-like destructive and invasive characteristics [ 15 , 16 ]. The phenotype, behavior, and role of FLSs in RA resemble the fundamental role of cancer-associated fibroblasts (CAFs) in various cancers [ 17 , 18 ]. In this article, we aimed to review the FLS transformation in RA, tumor-like behaviors of RA FLSs, and discuss the underlying mechanisms in three principal axes of metabolism, genetics, and epigenetic modifications (Fig.…”

Section: Introductionmentioning

confidence: 99%

Transformation of fibroblast‐like synoviocytes in rheumatoid arthritis; from a friend to foe

Mousavi

Karami

Aslani

et al. 2021

Autoimmun Highlights

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Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs’ phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.

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“…Through the interaction with T cells, B cells, macrophages and many pro-inflammatory cytokines, FLSs play an essential role in the pathogenesis of the disease and promote the continued joint inflammation [5], [6], [7], [8]. As a major source of inflammatory cytokines and catabolic enzymes that promote joint degeneration, RA-FLSs also exhibit some tumor-like behavior when activated in the chronic inflammatory environment, such as contact inhibition escape, anchorage-independent growth and increased ability of migration and invasion [9], [10], [11]. This transition behavior stimulates the progression of RA and eventually gives rise to joint destruction [12].…”

Section: Introductionmentioning

confidence: 99%

LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis

Guo

et al. 2019

EBioMedicine

131

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BackgroundLong non-coding RNAs (lncRNAs) have drawn increasing attention because they play a pivotal role in various types of autoimmune diseases, including rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs), a prominent component of hyperplastic synovial pannus tissue, are the primary effector cells in RA synovial hyperplasia and invasion which can lead to joint destruction. In this study, we investigated whether lncRNAs could act as competing endogenous RNAs to regulate the pathological behaviors of RA-FLSs.MethodsLncRNA microarray was conducted to establish lncRNA expression profiles in FLSs isolated from RA patients and healthy controls (HCs). Differentially expressed lncRNAs were verified by quantitative real-time PCR (qRT-PCR) on RA-FLSs and synovial fluid. The functional role of lncRNA PICSAR downregulation was evaluated in RA-FLSs. We conducted molecular biological analysis to predict miRNAs which have a potential binding site for PICSAR and further refined the results by qRT-PCR. Luciferase reporter assay was adopted to validate the interaction of lncRNA PICSAR and miR-4701-5p. Western Blot and qPCR were used to identify the target gene and protein. The functional role of miR-4701-5p upregulation was examined in RA-FLSs.FindingsWe identified a long intergenic non-protein-coding RNA162 (LINC00162), also known as lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA), has significantly higher expression in RA-FLSs and RA synovial fluid. The cell proliferation, migration, invasion and proinflammatory cytokines production of RA-FLSs showed significant alterations after the lncRNA PICSAR suppression. Mechanistically, lncRNA PICSAR functioned through sponging miR-4701-5p in RA-FLSs.InterpretationOur results reveal PICSAR may exert an essential role in promoting synovial invasion and joint destruction by sponging miR-4701-5p in RA and that lncRNA PICSAR may act as a biomarker of RA.

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Regulation of fibroblast-like synoviocyte transformation by transcription factors in arthritic diseases

Cited by 17 publications

References 102 publications

Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches

Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches

Transformation of fibroblast‐like synoviocytes in rheumatoid arthritis; from a friend to foe

LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis

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