Functional role of MIR-140 and MIR-146A in inflammation and catabolic processes in osteoarthritis

骨关节炎 炎症 小RNA 软骨 阿达姆斯 发病机制 滑膜关节 医学 基质金属蛋白酶 纤维化 滑液 细胞外基质 免疫学 病理 癌症研究 内科学 细胞生物学 金属蛋白酶 关节软骨 生物 基因 解剖 血栓反应素 替代医学 生物化学
作者
Ioanna V. Papathanasiou,Evanthia Mourmoura,Konstantinos N. Malizos,Aspasia Tsezou
出处
期刊:Osteoarthritis and Cartilage [Elsevier BV]
卷期号:27: S284-S284 被引量:2
标识
DOI:10.1016/j.joca.2019.02.668
摘要

Purpose: Osteoarthritis (OA) is a whole-joint disorder that is characterized by the loss of articular cartilage of synovial joints, synovial inflammation, subchondral bone remodelling and ligament fibrosis. MicroRNAs (miRNAs) play a prominent role in skeletal development and their abnormal expression has been suggested to contribute to pathogenic alterations of the OA joint. MiR-140 and miR-146a are expressed in cartilage tissue and control the extracellular matrix remodeling and inflammation responses in articular cartilage through genes’ regulation participating in signaling pathways, such as the Toll-like receptor 4 (TLR-4). TLR-4 signaling pathway is over activated in OA resulting in MMPs and cytokines upregulation and subsequent cartilage degradation. The aim of the present study was to investigate the functional role of miR-140 and miR-146a in inflammation and catabolic processes contributing to OA pathogenesis. Methods: Articular osteoarthritic and normal cartilage were obtained from 20 patients with primary osteoarthritis and 12 individuals with no history of joint disease, respectively. MiR-140 and miR-146a expression levels were investigated using quantitative real-time PCR. Bioinformatics analysis was used to investigate the target genes of the above microRNAs and their involved pathways. OA cultured chondrocytes were treated with miR-140 and/or miR-146a mimic and the expression levels of TLR-4, IRAK-1, TRAF-6, IL-1β, IL-6, IL-8, TNF-a, ADAMTS-5 and MMP-13 were evaluated using quantitative real-time PCR. Results: We observed that miR-140 and miR-146a expression levels were significantly reduced in OA compared with normal chondrocytes. Bioinformatics analysis revealed that the target genes of miR-140 and miR-146 are involved in common signaling pathways associated with OA, including inflammatory pathways, such as the TLR signaling. In TLR signaling, miR-140 regulates TLR-4 expression, whereas miR-146a participates in regulation of TLR-4 signaling though targeting IRAK-1 and TRAF-6. In addition, we confirmed the regulation of TLR-4 signaling by miR-140 and miR-146a at the cellular level, as we observed down-regulation of TLR-4 expression in OA chondrocytes after miR-140 treatment, whereas a significant reduction in IRAK-1 and TRAF-6 expression was found in miR-146a-treated OA chondrocytes compared to untreated. Moreover, we found that IL-6, IL-8, ADAMTS-5 and MMP-13, all targets of TLR-4 signaling, were decreased in miR-140 and miR-146a co-treated OA chondrocytes compared to untreated. Conclusions: Our study demonstrated, for the first time, the synergistic role of miR-140 and miR-146a in OA pathogenesis through targeting the TLR-4 signaling and modulating IL-6, IL-8, ADAMTS-5 and MMP-13 expression involved in inflammation and cartilage catabolism. As miR-140 and miR-146a are crucial regulators of processes involved in OA pathogenesis, modulation of their expression in OA may be a new strategy for treating osteoarthritic patients.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
mengwensi完成签到,获得积分10
刚刚
fu发布了新的文献求助10
刚刚
Hello应助靓丽的寒蕾采纳,获得10
1秒前
董怜寒发布了新的文献求助10
1秒前
1秒前
忆之完成签到,获得积分10
1秒前
2秒前
SciGPT应助勋xxx采纳,获得10
2秒前
稳重十三发布了新的文献求助20
2秒前
XHH1994发布了新的文献求助10
3秒前
乐乐应助怕黑以筠采纳,获得10
3秒前
tuntunliu完成签到,获得积分10
4秒前
罐罐发布了新的文献求助10
4秒前
4秒前
4秒前
李杍木发布了新的文献求助10
6秒前
6秒前
爱啥啥发布了新的文献求助10
6秒前
6秒前
科研通AI2S应助cadnash采纳,获得10
6秒前
wangbq完成签到 ,获得积分10
6秒前
Re关闭了Re文献求助
6秒前
cinq001发布了新的文献求助30
7秒前
7秒前
丘比特应助芷莯采纳,获得10
7秒前
8秒前
李顺杰完成签到,获得积分10
8秒前
8秒前
9秒前
9秒前
菜鸟完成签到,获得积分10
10秒前
疯狂的鲜花完成签到,获得积分10
10秒前
10秒前
机灵非笑完成签到,获得积分10
10秒前
10秒前
王相博发布了新的文献求助10
10秒前
10秒前
师霸完成签到,获得积分10
11秒前
CipherSage应助自由的聋五采纳,获得10
11秒前
HongMou完成签到 ,获得积分10
11秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970240
求助须知:如何正确求助?哪些是违规求助? 3514997
关于积分的说明 11176725
捐赠科研通 3250268
什么是DOI,文献DOI怎么找? 1795244
邀请新用户注册赠送积分活动 875725
科研通“疑难数据库(出版商)”最低求助积分说明 805004