The inflammatory circuitry of miR-149 as a pathological mechanism in osteoarthritis

被引：105

作者：

Santini P. ^{[1
]}

Politi L. ^{[1
]}

Vedova P.D. ^{[2
]}

Scandurra R. ^{[1
]}

Scotto D'Abusco A. ^{[1
]}

机构：

[1] Department of Biochemical Sciences, Sapienza Università di Roma, 00185 Rome, P.le A. Moro

[2] Ospedale S. Giuseppe, Albano Laziale, ASL RMH, Rome

来源：

Rheumatology International | 2014年 / 34卷 / 5期

关键词：

Cytokines; Inflammation; MicroRNA; Ostearthritis;

D O I：

10.1007/s00296-013-2754-8

中图分类号：

学科分类号：

摘要：

Osteoarthritis (OA) is a multifactorial degenerative pathology, whose progression is exacerbated by pro-inflammatory cytokines signaling. Among the changes triggered in chondrocytes during inflammation, modified expression of tiny epigenetic regulators as microRNAs was shown having deleterious implications for articular cartilage. Aim of the present study was to identify differentially expressed microRNAs in human OA cartilage and to determine their relevance to pathological progression. An OA model based on inflammatory stimulation of a chondrocytic human cell line was used to analyze microRNAs deregulation, and results revealed miR-149 severely down-regulated by IL1β and TNFα. Real-time PCR analysis of miR-149 was exerted also in human primary chondrocytes isolated from cartilage of OA donors and postmortem from subjects with no known history of OA, confirming down-regulation in osteoarthritis. Moving on a functional study, miR-149 regulatory effect on tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1β) and interleukin 6 (IL6) 3′UTRs was evaluated by luciferase assays, and chondrocytes production of TNFα upon miR-149 transfection was measured by enzyme-linked immuno sorbent assay. We found that miR-149 is down-regulated in OA chondrocytes, and this decrease seems to be correlated to increased expression of pro-inflammatory cytokines such as TNFα, IL1β and IL6. OA is a multifactorial disease and we think that our results give new insights for understanding the complex mechanisms of osteoarthritic pathogenesis. © 2013 Springer-Verlag.

引用

页码：711 / 716

页数：5

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