Extracellular miR-574-5p Induces Osteoclast Differentiation via TLR 7/8 in Rheumatoid Arthritis

Hegewald, Anett B.; Breitwieser, Kai; Ottinger, Sarah M.; Mobarrez, Fariborz; Korotkova, Marina; Réthi, Bence; Jakobsson, Per‐Johan; Catrina, Anca I.; Wähämaa, Heidi; Saul, Meike J.

doi:10.3389/fimmu.2020.585282

Cited by 38 publications

(42 citation statements)

References 50 publications

(65 reference statements)

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“…Hsa-miR-574-5P, also known as miR-574-5P, has been studied as cancer biomarker for several human tumors like lung (41), colorectal (42), and squamous cell carcinoma (43). It is also known to be affected in other conditions such as rheumatoid arthritis (44), and diabetes mellitus (45). Other hub miRNAs including hsa-miR-1827, and hsa-miR-4429 have been associated with particular various types of cancers.…”

Section: Discussionmentioning

confidence: 99%

MiR-574-5P, miR-1827, And miR-4429 As Potential Biomarkers For Schizophrenia

Davarinejad

Najafi

Zhaleh

et al. 2021

Preprint

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Schizophrenia is a severe chronic debilitating disorder with millions of affected individuals. Lack of a reliable mollecular diagnostic invokes the identification of novel biomarkers. To elucidate the molecular basis of the disease, two mRNA expression arrays including GSE93987 and GSE38485, and one miRNA array, GSE54914, were downloaded from GEO, and meta-analysis was performed for mRNA expression arrays by employment of metaDE package. By WGCNA package, we performed network analysis for both mRNA expression arrays separately. Then, we made protein-protein interaction network for significant modules. Limma package was employed to analyze the miRNA array and dysregulated miRNAs (DEMs) were identified. Using genes of significant modules and DEMs, a mRNA-miRNA network was constructed and hub genes and miRNAs were identified. To confirm the dysregulation of genes, expression values were evaluated by available datasets including GEO series GSE62333, GSE93987, and GSE38485. The ability of the detected hub miRNAs to discriminate Schizophrenia from healthy controls was evaluated by assessing the receiver-operating curve. Finally, by performing Real-Time PCR, the expression level of genes and miRNAs were evaluated in 40 Schizophrenia patients compared with healthy controls. The results confirmed dysregulation of hsa-miR-574-5P, hsa-miR-1827, hsa-miR-4429, CREBRF, ARPP19, TGFBR2, and YWHAZ in blood samples of schizophrenia patients.

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Section: Discussionmentioning

confidence: 99%

MiR-574-5P, miR-1827, And miR-4429 As Potential Biomarkers For Schizophrenia

Davarinejad

Najafi

Zhaleh

et al. 2021

Preprint

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“…86 Furthermore, FLS from ACPA+ patients release extracellular vesicles containing miR-574-5p, which activates TLR7 and TLR8 to induce osteoclastogenesis. 87 Similarly, miR-let-7b can activate TLR7 on monocytes to induce TNF and IL-6 and promote differentiation to M1 macrophages when released in extracellular vesicles by synovial fluid macrophages. 88 Experimental arthritis models have also indicated a pathogenic role for TLR7 and TLR8.…”

Section: Tlr7 and Tlr8mentioning

confidence: 99%

“… 93 Inhibition of TLR4 suppresses disease and reduces cytokine release from FLS in the AIA rat model. 74 Osteoclasto-genesis TLR2, 42 TLR3, 58 TLR5, 78 TLR7 and TLR8 87 TLR4 (CIA model), 70 TLR5 (CIA model) 78 and TLR9 (rat PIA model) 99 Cell invasion/ migration TLR2 44 , 45 TLR5 78 Abbreviations: AIA, adjuvant induced-arthritis; CIA, collagen-induced arthritis; DAS28, disease activity score 28; FLS, fibroblast-like synoviocytes; hTLR8tg, human TLR8 transgenic; IL, interleukin; IL-1Ra, IL-1 receptor antagonist; M1V, methionine1valine; miRNA, microRNA; NK cells, natural killer cells; PBMCs, peripheral blood mononuclear cells; PIA, pristane-induced arthritis; RA, rheumatoid arthritis; SCW, streptococcal cell wall; SF, synovial fluid; TLR, toll-like receptor; ↑, upregulated; ↓, downregulated. …”

Section: Tlrs In Ramentioning

confidence: 99%

Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology

Unterberger¹,

Davies²,

Rambhatla³

et al. 2021

ITT

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Rheumatoid arthritis (RA) is a progressive autoimmune disease that is characterized by inflammation of the synovial joints leading to cartilage and bone damage. The pathogenesis is sustained by the production of pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6, which can be targeted therapeutically to alleviate disease severity. Several innate immune receptors are suggested to contribute to the chronic inflammation in RA, through the production of pro-inflammatory factors in response to endogenous danger signals. Much research has focused on toll-like receptors and more recently the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 (NLRP3) inflammasome, which is required for the processing and release of IL-1β. This review summarizes the current understanding of the potential involvement of these receptors in the initiation and maintenance of inflammation and tissue damage in RA and experimental arthritis models.

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“…This is a non-coding RNA carried by cell-derived small extracellular vesicles that mediate cell-to-cell communication in the synovial microenvironment. This novel mechanism underlying the pathogenesis of RA points to miR-574-5p as a target to protect against osteoclast mediated cartilage destruction [ 70 , 71 ]. Further, a MiR-147 mimic suppressed the expression of TLR7 in a pristane-induced arthritic rat model and improved the severity of arthritis [ 72 ].…”

Section: Synthetic Ligands That Down-regulate Tlr Activitymentioning

confidence: 99%

Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?

Santos-Sierra

2021

Biomolecules

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Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one’s self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs (e.g., joints, lungs, heart, eyes). Different medications to control the excessive immune response are in use, however, drug resistances, flare-reactions and adverse effects to the current therapies are common in the affected patients. Thus, it is essential to broaden the spectrum of alternative treatments and to develop disease-modifying drugs. In the last 20 years, the involvement of the innate immune receptors TLRs in inflammatory arthritis has been widely investigated and targeting either the receptor itself or the proteins in the downstream signalling cascades has emerged as a promising therapeutic strategy. Yet, concerns about the use of pharmacological agents that inhibit TLR activity and may leave the host unprotected against invading pathogens and toxicity issues amid inhibition of downstream kinases crucial in various cellular functions have arisen. This review summarizes the existing knowledge on the role of TLRs in inflammatory arthritis; in addition, the likely druggable related targets and the developed inhibitors, and discusses the pros and cons of their potential clinical use.

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Extracellular miR-574-5p Induces Osteoclast Differentiation via TLR 7/8 in Rheumatoid Arthritis

Cited by 38 publications

References 50 publications

MiR-574-5P, miR-1827, And miR-4429 As Potential Biomarkers For Schizophrenia

MiR-574-5P, miR-1827, And miR-4429 As Potential Biomarkers For Schizophrenia

Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology

Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?

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