MiR-613 inhibits proliferation and invasion and induces apoptosis of rheumatoid arthritis synovial fibroblasts by direct down-regulation of DKK1

Abstract

Background This study aimed to investigate the effects of miR-613 on the proliferation, invasion and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs). Methods Synovial tissue samples were collected from 20 rheumatoid arthritis (RA) patients and 10 patients with joint trauma undergoing joint replacement surgery. The RASFs were isolated and cultured. MiR-613 and DKK1 expression in both synovial tissues and cells was detected using quantitative real-time PCR (qRT-PCR). Dual luciferase reporter gene assay was employed to evaluate the effect of miR-613 on the luciferase activity of DKK1. Then RASFs were transfected with miR-613 mimics, si-DKK1 and pcDNA-DKK1. Changes in cellular proliferation, invasion and apoptosis were detected through BrdU assay, Transwell invasion assay and flow cytometry analysis, respectively. Results MiR-613 was significantly down-regulated in RA tissues and RASFs compared to normal tissues and cells, whereas DKK1 was up-regulated in RA tissues and RASFs. Dual luciferase reporter gene assay showed that miR-613 could specifically bind to the 3′UTR of DKK1 and significantly inhibit the luciferase activity. Moreover, miR-613 significantly reduced the expression of DKK1. Overexpression of miR-613 or knockdown of DKK1 suppressed proliferation and invasion of RASFs, and induced RASF apoptosis. The reverse results were observed when DKK1 was up-regulated in miR-613-overexpressing RASFs. Conclusions MiR-613 can inhibit proliferation and invasion and induce apoptosis of RASFs by directly targeting DKK1 expression.

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

“…Such cellular events are mainly mediated through excessive release of inflammatory cytokines and RANKL that elevate the proteolytic activity of osteoclasts at the joint 59 . The Wnt1/β‐catenin signalling is known to be naturally suppressed by both LRP inhibitor (Dickkopf homolog 1 [DKK1]) and Dvl‐1 inhibitor (CYLD; a cell cycle regulator) that lead to the dormancy of β‐catenin inside the FLS cells, while are repressed in FLS cells during RA condition 60‐62 …”

“…Such cellular events are mainly mediated through excessive release of inflammatory cytokines and RANKL that elevate the proteolytic activity of osteoclasts at the joint. 59 The Wnt1/β-catenin signalling is known to be naturally suppressed by both LRP inhibitor (Dickkopf homolog 1 [DKK1]) and Dvl-1 inhibitor (CYLD; a cell cycle regulator) that lead to the dormancy of β-catenin inside the FLS cells, while are repressed in FLS cells during RA condition [60][61][62]. Recent research reveals that berberine suppresses the Wnt1/βcatenin signalling in AAFLS cells by decreasing the levels of FZD4, LRP5 and Dvl-1 via inducing CYLD, which result in the decreased levels of β-catenin.…”

Interleukin 6 Metabolism and Functional Kidney Status in Early Rheumatoid Arthritis

“…До останнього часу не піддавалась сумніву виправданість хірургічної тактики при паранеф-ральному абсцесі. Однак, з удосконаленням методів візуалізації та впровадженням у клінічну практику малоінвазивних технологій відкриваються нові перспективи у лікуванні зазначених хворих [4,5].…”

“…При РА головним місцем синтезу як основних прозапальних, так і деяких протизапальних цитокінів є синовіальна тканина, водночас їх концентрація зростає і в синовіальній рідині. Головними їх продуцентами є макрофаги, фібробласти і Т-клітини [5]. Зв'язування цитокінів із рецептором через ряд проміжних стадій призводить до активації транскрипції виділених генів.…”

Dysregulated microRNA expression in rheumatoid arthritis families—a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls

“…In a recent study based on indigenous North Americans, Anaparti et al have shown an altered expression of several microRNAs in blood samples of RA patients as well as their FDRs, compared to healthy controls (HCs) [5]. Several other studies have similarly identified a dysregulated expression of microRNAs within the inflamed joints [7][8][9][10] and serum [11] as well as peripheral blood mononuclear cells (PBMCs) [12] from patients with RA, indicating that microRNA might have a role in the pathogenesis of the disease.…”