Abstract:
INTRODUCTION:Anti-malarial drug artesunate can suppress inflammation and prevent cartilage and bone destruction in collagen-induced arthritis model in rats-suggesting it may be a potent drug for rheumatoid arthritis (RA) therapy. We aimed to investigate its effect on the invasive property of fibroblast-like synoviocytes (FLS) from patients with RA. METHODS:Synovial tissues were obtained by closed needle biopsy from active RA patients, and FLS were isolated and cultured in vitro. RA-FLS were treated with artesunate at various concentrations, while methotrexate or hydroxychloroquine was employed as comparator drugs. Cell viability, proliferation, cell cycle, apoptosis, migration, invasion, and pseudopodium formation of RA-FLS were assessed by CCK-8 assays, EdU staining, Annexin V-FITC/PI staining, transwell assays, or F-actin staining, respectively. Further, relative changes of expressed proteases were analyzed by Proteome profiler human protease array and verified by quantitative real-time PCR (qPCR), Western blot, and ELISA. The expression of signaling molecules of MAPK, NF-κB, AP-1, and PI3K/Akt pathways were measured by qPCR and Western blot. PDK-1 knockdown by specific inhibitor AR-12 or siRNA transfection was used to verify the pharmacological mechanism of artesunate on RA-FLS. RESULTS:Artesunate significantly inhibited the migration and invasion of RA-FLS in a dose-dependent manner with or without TNF-α stimulation. The effect was mediated through artesunate inhibition of MMP-2 and MMP-9 production, and pre-treatment with exogenous MMP-9 reversed the inhibitory effect of artesunate on RA-FLS invasion. Artesunate had a stronger inhibitory effect on migration and invasion of RA-FLS as well as greater anti-inflammatory effect than those of hydroxychloroquine. Similar inhibitory effect was detected between artesunate and methotrexate, and synergy was observed when combined. Mechanistically, artesunate significantly inhibited PDK-1 expression as well as Akt and RSK2 phosphorylation-in a similar manner to PDK-1-specific inhibitor AR-12 or PDK-1 knockdown by siRNA transfection. This inhibition results in suppression of RA-FLS migration and invasion as well as decreased MMP-2 and MMP-9 expression. CONCLUSIONS:Our study demonstrates artesunate is capable of inhibiting migration and invasion of RA-FLS through suppression of PDK1-induced activation of Akt and RSK2 phosphorylation-suggesting that artesunate may be a potential disease-modifying anti-rheumatic drug for RA.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Ma JD,Jing J,Wang JW,Yan T,Li QH,Mo YQ,Zheng DH,Gao JL,Nguyen KA,Dai Ldoi
10.1186/s13075-019-1935-6subject
Has Abstractpub_date
2019-06-24 00:00:00pages
153issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-019-1935-6journal_volume
21pub_type
杂志文章abstract:INTRODUCTION:The present study examined the effect of C-type natriuretic peptide (CNP) on the anabolic and catabolic activities in chondrocyte/agarose constructs subjected to dynamic compression. METHODS:Constructs were cultured under free-swelling conditions or subjected to dynamic compression with low (0.1 to 100 pM...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3459
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:The aim of this study was to develop a patient-reported questionnaire that is suitable to detect periodontitis (PD) in patients with rheumatoid arthritis (RA). METHODS:A self-reported questionnaire containing 12 items potentially relevant to PD and dentists' semiquantitative assessment of PD (no/mild/modera...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-019-1982-z
更新日期:2019-08-29 00:00:00
abstract:INTRODUCTION:In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To cl...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4345
更新日期:2013-10-24 00:00:00
abstract:INTRODUCTION:Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs. METHODS:In total, 394 older men and women (mean age, 63 years; range, 52 ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3689
更新日期:2012-01-18 00:00:00
abstract::The present studies were initiated to determine the protein expression patterns of fibroblast-like synovial (FLS) cells derived from the synovia of rheumatoid arthritis patients. The cellular proteins were separated by two-dimensional polyacrylamide gel electrophoresis and the in-gel digested proteins were analyzed by...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1153
更新日期:2004-01-01 00:00:00
abstract::Rheumatoid arthritis (RA) is a systemic autoimmune disease manifesting in joint destruction. The recognized hallmark of RA pathogenesis is the involvement of immune cells which produce many mediators potentiating an inflammatory environment. RA synovial fibroblasts (RASFs) contribute significantly to disease progressi...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/s13075-015-0846-4
更新日期:2015-11-06 00:00:00
abstract:INTRODUCTION:A proliferation-inducing ligand (APRIL) from the TNF family, owing to its role in the generation and survival of plasma cells (PCs), is currently targeted for rheumatoid arthritis (RA) treatment. However, little is known about APRIL expression in RA lesions, hampering our understanding of the way APRIL may...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2817
更新日期:2009-01-01 00:00:00
abstract::The objective of this study was to evaluate the safety and possible efficacy of IFN-beta-1a for the treatment of patients with rheumatoid arthritis (RA). Twenty-two patients with active RA were enrolled in a phase II randomized, double-blind, placebo-controlled trial of 30 microg IFN-beta-1a by weekly self-injection f...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1026
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from A...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2929
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The high-affinity receptor for IgG Fcgamma/CD64 is critical for the development of lupus nephritis (LN). Cross-linking Fc receptor on recruited monocytes by IgG-containing immune complexes is a key step in immune-complex-mediated nephritis in systemic lupus erythematosus (SLE). The goal of this study was t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2590
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients wi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3873
更新日期:2012-06-12 00:00:00
abstract:INTRODUCTION:Our objectives were to examine mononuclear cell gene expression profiles in patients with systemic lupus erythematosus (SLE) and healthy controls and to compare subsets with and without atherosclerosis to determine which genes' expression is related to atherosclerosis in SLE. METHODS:Monocytes were obtain...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4609
更新日期:2014-07-10 00:00:00
abstract:INTRODUCTION:Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4065
更新日期:2012-10-18 00:00:00
abstract:INTRODUCTION:Angiogenesis plays a critical role in synovial inflammation and joint destruction in rheumatoid arthritis (RA). Vascular endothelial growth factor A (VEGF-A) and angiopoietins are two important mediators of synovial angiogenesis. We have previously developed a novel chimeric decoy receptor, namely, double-...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4265
更新日期:2013-08-14 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4465
更新日期:2014-01-31 00:00:00
abstract::Cardiovascular morbidity and mortality are becoming major health concerns for adults with inflammatory rheumatic diseases. The enhanced atherogenesis in this patient population is promoted by the exposure to traditional risk factors as well as nontraditional cardiovascular insults, such as corticosteroid therapy, chro...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4212
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great v...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02218-8
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:This study aimed at investigating the effect of a resistance exercise intervention on the interstitial muscle levels of pro-inflammatory cytokines in fibromyalgia (FMS) and healthy controls (CON). METHODS:Twenty-four female patients with FMS (54 ± 8 years) and 27 female CON (54 ± 9 years) were subjected to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13075-016-1041-y
更新日期:2016-06-13 00:00:00
abstract:INTRODUCTION:Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/ar2740
更新日期:2009-01-01 00:00:00
abstract::The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3204
更新日期:2011-02-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3087
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The important functions of the meniscus are shock absorption, passive stabilization and load transmission of the knee. Because of the avascularity of two-thirds of the meniscal center region, the treatment of tears in this area is hard. Recently, microRNAs have been proven to play an important role in the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0488-y
更新日期:2014-11-28 00:00:00
abstract:BACKGROUND:In this study, we evaluated the impact of obesity and/or overweight on the achievement of minimal disease activity (MDA) in patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) receiving an anti-rheumatic treatment. Obesity can be considered a low-grade, chronic systemic inflam...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
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更新日期:2016-12-13 00:00:00
abstract::Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting high amounts of inflammatory cytokines. It is a frequent manifestation in patients with predisposing genetic defects, but can o...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3843
更新日期:2012-06-08 00:00:00
abstract::The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. The cells were isolated from human articular cartilage obtained at surgery and were cultured in the absence or presence of ET-1 with or without inhibi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1489
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0632-3
更新日期:2015-05-21 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3764
更新日期:2012-03-06 00:00:00
abstract::The relationship between serum urate, menopause, and aging has not been clearly defined by scientific evidence. In the present issue of Arthritis Research and Therapy, Hak and Choi present a cross-sectional analysis to clarify the effect of menopause and hormone replacement therapy on serum urate in women within the T...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2524
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:The aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies. METHODS:Patients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13075-018-1541-z
更新日期:2018-03-23 00:00:00