Synovial fibroblast-derived exosomal microRNA-106b suppresses chondrocyte proliferation and migration in rheumatoid arthritis via down-regulation of PDK4

Liú, Dan; Fang, Yu; Rao, Yujun; Tan, Wei; Zhou, Wei; Wu, Xia; Zhang, Chunwang; Zhang, Yu; Liu, Yanqing; Sunagawa, Makoto; Hisamitsu, Tadashi; Li, Guoqing

doi:10.1007/s00109-020-01882-2

Cited by 33 publications

(20 citation statements)

References 52 publications

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“…This phenomenon may be attributed to lncRNA Hotair that regulates the activation of NF- κ B and the expression of its target genes (IL-6 and iNOS) by promoting I κ B α degradation [ 49 ]. In rheumatoid arthritis, miR-106b is highly expressed in fibroblast-derived exosomes [ 50 ]. miR-106b promotes macrophage polarization and increases osteoclast formation by activating phosphatase and tensin homolog/phosphatidylinositol 3-kinase/serine/threonine-protein kinase (PTEN/PI3K/AKT) and NF- κ B signaling pathways [ 51 ].…”

Section: Exosomes and Macrophage Polarizationmentioning

confidence: 99%

[Retracted] Exosome: Function and Application in Inflammatory Bone Diseases

Wang

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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In the skeletal system, inflammation is closely associated with many skeletal disorders, including periprosthetic osteolysis (bone loss around orthopedic implants), osteoporosis, and rheumatoid arthritis. These diseases, referred to as inflammatory bone diseases, are caused by various oxidative stress factors in the body, resulting in long-term chronic inflammatory processes and eventually causing disturbances in bone metabolism, increased osteoclast activity, and decreased osteoblast activity, thereby leading to osteolysis. Inflammatory bone diseases caused by nonbacterial factors include inflammation- and bone resorption-related processes. A growing number of studies show that exosomes play an essential role in developing and progressing inflammatory bone diseases. Mechanistically, exosomes are involved in the onset and progression of inflammatory bone disease and promote inflammatory osteolysis, but specific types of exosomes are also involved in inhibiting this process. Exosomal regulation of the NF-κB signaling pathway affects macrophage polarization and regulates inflammatory responses. The inflammatory response further causes alterations in cytokine and exosome secretion. These signals regulate osteoclast differentiation through the receptor activator of the nuclear factor-kappaB ligand pathway and affect osteoblast activity through the Wnt pathway and the transcription factor Runx2, thereby influencing bone metabolism. Overall, enhanced bone resorption dominates the overall mechanism, and over time, this imbalance leads to chronic osteolysis. Understanding the role of exosomes may provide new perspectives on their influence on bone metabolism in inflammatory bone diseases. At the same time, exosomes have a promising future in diagnosing and treating inflammatory bone disease due to their unique properties.

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Section: Exosomes and Macrophage Polarizationmentioning

confidence: 99%

[Retracted] Exosome: Function and Application in Inflammatory Bone Diseases

Wang

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Significantly, the disturbed synovial fibroblast-derived exosomal miRNAs were discovered in recent years. Liu et al demonstrated that the expression level of miRNA miR-106b was significantly increased in synovial fluid-derived exosomes of RA, and it could target the pyruvate dehydrogenase kinase 4 (PDK4) gene; it could attenuate RA progression by regulating chondrocyte proliferation and migration (47). Furthermore, research found that RA synovial fibroblast (RASF)-exosomal miR-146a, miR-155, miR-323a, and miR-1307 are also involved in inducing local inflammation and attenuating octeoclastogenesis in RA (103).…”

Section: Introductionmentioning

confidence: 99%

Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis

2022

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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that affect synovitis, bone, cartilage, and joint. RA leads to bone and cartilage damage and extra-articular disorders. However, the pathogenesis of RA is still unclear, and the lack of effective early diagnosis and treatment causes severe disability, and ultimately, early death. Accumulating evidence revealed that the regulatory network that includes long non-coding RNAs (lncRNAs)/circular RNAs (circRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNA) plays important roles in regulating the pathological and physiological processes in RA. lncRNAs/circRNAs act as the miRNA sponge and competitively bind to miRNA to regulate the expression mRNA in synovial tissue, FLS, and PBMC, participate in the regulation of proliferation, apoptosis, invasion, and inflammatory response. Thereby providing new strategies for its diagnosis and treatment. In this review, we comprehensively summarized the regulatory mechanisms of lncRNA/circRNA-miRNA-mRNA network and the potential roles of non-coding RNAs as biomarkers and therapeutic targets for the diagnosis and treatment of RA.

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“…Genes associated with cartilage homeostasis were also upregulated in infiltrating leukocytes isolated from IL-17A/F–treated mice: PDK4, which encodes pyruvate dehydrogenase kinase 4, is required for chondrocyte proliferation and is suppressed in RA joints [ 113 ], while GLUL, which encodes glutamine synthetase, has been shown to be downregulated in cartilage from patients with severe osteoarthritis [ 114 ]. This information is of particular relevance as our data also indicates that cartilage damage is substantially reduced in RRV-infected mice treated with anti-IL-17A/F antibody.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-17 contributes to Ross River virus-induced arthritis and myositis

et al. 2022

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Arthritogenic alphaviruses are mosquito-borne viruses that are a major cause of infectious arthropathies worldwide, and recent outbreaks of chikungunya virus and Ross River virus (RRV) infections highlight the need for robust intervention strategies. Alphaviral arthritis can persist for months after the initial acute disease, and is mediated by cellular immune responses. A common strategy to limit inflammation and pathology is to dampen the overwhelming inflammatory responses by modulating proinflammatory cytokine pathways. Here, we investigate the contribution of interleukin-17 (IL-17), a cytokine involved in arthropathies such as rheumatoid arthritis, in the development RRV-induced arthritis and myositis. IL-17 was quantified in serum from RRV-infected patients, and mice were infected with RRV and joints and muscle tissues collected to analyse cellular infiltrates, tissue mRNA, cytokine expression, and joint and muscle histopathology. IL-17 expression was increased in musculoskeletal tissues and serum of RRV-infected mice and humans, respectively. IL-17–producing T cells and neutrophils contributed to the cellular infiltrate in the joint and muscle tissue during acute RRV disease in mice. Blockade of IL-17A/F using a monoclonal antibody (mAb) reduced disease severity in RRV-infected mice and led to decreased proinflammatory proteins, cellular infiltration in synovial tissues and cartilage damage, without affecting viral titers in inflamed tissues. IL-17A/F blockade triggered a shift in transcriptional profile of both leukocyte infiltrates and musculoskeletal stromal cells by downregulating proinflammatory genes. This study highlights a previously uncharacterized role for an effector cytokine in alphaviral pathology and points towards potential therapeutic benefit in targeting IL-17 to treat patients presenting with RRV-induced arthropathy.

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Synovial fibroblast-derived exosomal microRNA-106b suppresses chondrocyte proliferation and migration in rheumatoid arthritis via down-regulation of PDK4

Cited by 33 publications

References 52 publications

[Retracted] Exosome: Function and Application in Inflammatory Bone Diseases

[Retracted] Exosome: Function and Application in Inflammatory Bone Diseases

Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis

Interleukin-17 contributes to Ross River virus-induced arthritis and myositis

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