Disorders of MicroRNAs in Peripheral Blood Mononuclear Cells: As Novel Biomarkers of Ankylosing Spondylitis and Provocative Therapeutic Targets

Lv, Qing; Li, Qiuxia; Zhang, Pei-Zhuo; Jiang, Yongluo; Wang, Xinwei; Wei, Qiujing; Cao, Shuangyan; Liao, Zetao; Lin, Zhiming; Pan, Yunfeng; Huang, Jianlin; Li, Tianwang; Jin, Ou; Wu, Yuqiong; J, Gu

doi:10.1155/2015/504208

Cited by 26 publications

(17 citation statements)

References 26 publications

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“…MiR‐27a and miR‐126‐3p, which have been previously reported as aberrantly expressed in patients with AS, were also verified upregulated in patients with nr‐axSpA rather than in healthy controls in our study. The relative expression of miR‐27a in patients with nr‐axSpA was slightly higher than in patients with AS, while miR‐126‐3p was expressed similar in both patients with nr‐axSpA and AS.…”

Section: Discussionsupporting

confidence: 83%

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Aberrant expression of microRNAs in peripheral blood mononuclear cells as candidate biomarkers in patients with axial spondyloarthritis

et al. 2019

Int J of Rheum Dis

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Objectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory arthritis involving the axial skeleton. Recent evidence suggests that microRNAs (miRNAs) play a critical role in ankylosing spondylitis (AS). In this study, we aimed to investigate whether miR-17-5p, miR-27a, miR-29a and miR-126-3p can be verified as potential biomarkers of axSpA. Methods: Peripheral blood mononuclear cell (PBMC) miRNA expression was evaluated by quantitative real-time polymerase chain reaction among 43 patients with AS, 26 patients with non-radiographic axSpA (nr-axSpA) and 39 healthy controls. Detailed clinical histories were recorded and the correlation of miRNAs and clinical features were analyzed.Results: When compared to controls, both patients with AS and nr-axSpA had significantly higher expression levels of miR-17-5p, miR-27a, miR-29a and miR-126-3p. MiR-27a was negatively correlated with Ankylosing Spondylitis Disease ActivityScore as well as C-reactive protein in patients with nr-axSpA (r = −0.51, P < 0.01 and r = −0.42, P = 0.034 respectively). No other clinical features were found to correlate with the four miRNAs in patients with AS. Mir-29a showed highest area under the curve with 0.952 and these four miRNAs may be potential biomarkers in patients with axSpA. Conclusions:We reported elevated miR-17-5p, miR-27a, miR-29a and miR-126-3p expression in PBMCs of patients with axSpA, and the expression of these four miRNAs might be used as useful diagnostic markers in axSpA. K E Y W O R D Sankylosing spondylitis, biological markers, microRNAs, non-radiographic axial spondyloarthritis

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Section: Discussionsupporting

confidence: 83%

“…On the basis of a previous study on microarray results, as well as verification experiments, miR‐17‐5p, miR‐27a, miR‐29a and miR‐126‐3p have been seen to be dysregulated in patients with AS. Thus, these four miRNAs were selected for further research.…”

Section: Introductionmentioning

confidence: 92%

Aberrant expression of microRNAs in peripheral blood mononuclear cells as candidate biomarkers in patients with axial spondyloarthritis

et al. 2019

Int J of Rheum Dis

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“…Studies have shown the association between miR-29a-3p and ankylosing spondylitis (AS) [28,29]. Although data on miR-29a-3p levels in AS are inconsistent, Prajzlerova et al reported that patients with advanced-stage AS with extensive bone formation have higher levels of TGF-β, as well as miR-29a suppression and increased bone formation [30].…”

Section: Discussionmentioning

confidence: 99%

Significant changes in synovial fluid microRNAs after high tibial osteotomy in medial compartmental knee osteoarthritis: Identification of potential prognostic biomarkers

Kwak

Kim

et al. 2020

PLoS ONE

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High tibial osteotomy (HTO) is a well-established treatment for medial compartmental knee osteoarthritis. Several microRNAs (miRNAs) are involved in osteoarthritis progression and are useful as osteoarthritis-related biomarkers. In this prospective study, we investigated differentially expressed microRNAs in the synovial fluid (SF) before and after HTO in patients with medial compartmental knee osteoarthritis to identify microRNAs that can be used as prognostic biomarkers. We used miRNA-PCR arrays to screen for miRNAs in SF samples obtained preoperatively and 6 months postoperatively from 6 patients with medial compartmental knee osteoarthritis who were treated with medial open wedge HTO. Differentially expressed miRNAs identified in the profiling stage were validated by real-time quantitative PCR in 22 other patients who had also been treated with HTO. All patients radiographically corresponded to Kellgren-Lawrence grade II or III with medial compartmental osteoarthritis. These patients were clinically assessed using a visual analogue scale and Western Ontario McMaster Universities scores. Mechanical axis changes were measured on standing anteroposterior radiographs of the lower limbs assessed preoperatively and at 6 months postoperatively. Among 84 miRNAs known to be involved in the inflammatory process, 14 were expressed in all SF specimens and 3 (miR-30a-5p, miR-29a-3p, and miR-30c-5p) were differentially expressed in the profiling stage. These 3 miRNAs, as well as 4 other miRNAs (miR-378a-5p, miR-140-3p, miR-23a-3p, miR-27b-3p), are related to osteoarthritis progression. These results were validated in the SF from 22 patients. Clinical and radiological outcomes improved after HTO in all patients, and only 2 miRNAs (miR-30c-5p and miR-23a-3p) were significantly differentially expressed between preoperative and postoperative 6month SF samples (p = 0.006 and 0.007, respectively). Of these two miRNAs, miR-30c-5p

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“…The data on miR-29a levels in AS are rather inconsistent. While miR-29a expression in peripheral blood mononuclear cells was lower in active AS patients than in controls and decreased after anti-TNF therapy [ 32 ], another showed otherwise [ 33 ]. TGF-β, an important stimulator of bone formation [ 34 ], inhibits miR-29a expression [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Association between circulating miRNAs and spinal involvement in patients with axial spondyloarthritis

et al. 2017

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ObjectivesDysregulation of miRNAs and their target genes contributes to the pathophysiology of autoimmune diseases. Circulating miRNAs may serve as diagnostic/prognostic biomarkers. We aimed to investigate the association between circulating miRNAs, disease activity and spinal involvement in patients with axial spondyloarthritis (AxSpA).MethodsTotal RNA was isolated from the plasma of patients with non-radiographic (nr)AxSpA, patients with ankylosing spondylitis (AS) and healthy controls (HC) via phenol-chloroform extraction. A total of 760 miRNAs were analysed with TaqMan® Low Density Arrays, and the expression of 21 miRNAs was assessed using single assays.ResultsComprehensive analysis demonstrated the differential expression of miRNAs among patients with progressive spinal disease. Of the 21 miRNAs selected according to their expression patterns, the levels of miR-625-3p were significantly different between nr-AxSpA patients and HCs. We found no correlation between miRNA levels and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in nr-AxSpA patients. Selected miRNAs, such as miR-29a-3p, miR-146a-5p or miR-222-3p with an established role in extracellular matrix formation and inflammation were associated with spinal changes and/or disease activity assessed by BASDAI in AS patients, including miR-625-3p reflecting disease activity in AS with spinal involvement.ConclusionsOur data indicate that circulating miRNAs play a role in the pathogenesis of AxSpA and are also suggestive of their potential as biomarkers of disease progression. We hypothesize that differential systemic levels of miRNA expression reflect miRNA dysregulation at sites of spinal inflammation or bone formation where these molecules contribute to the development of pathophysiological features typical of AxSpA.

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Disorders of MicroRNAs in Peripheral Blood Mononuclear Cells: As Novel Biomarkers of Ankylosing Spondylitis and Provocative Therapeutic Targets

Cited by 26 publications

References 26 publications

Aberrant expression of microRNAs in peripheral blood mononuclear cells as candidate biomarkers in patients with axial spondyloarthritis

Aberrant expression of microRNAs in peripheral blood mononuclear cells as candidate biomarkers in patients with axial spondyloarthritis

Significant changes in synovial fluid microRNAs after high tibial osteotomy in medial compartmental knee osteoarthritis: Identification of potential prognostic biomarkers

Association between circulating miRNAs and spinal involvement in patients with axial spondyloarthritis

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