MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses.
MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses.
复制标题
DOI：
10.1002/art.24745
复制
发表时间：
2009-09
影响因子：
--
通讯作者：
Asahara, Hiroshi
中科院分区：
文献类型：
--
作者：
Miyaki, Shigeru;Nakasa, Tomoyuki;Otsuki, Shuhei;Grogan, Shawn P.;Higashiyama, Reiji;Inoue, Atsushi;Kato, Yoshio;Sato, Tempei;Lotz, Martin K.;Asahara, Hiroshi
MicroRNAs （miRNAs）是一类非编码小rna，作为基因表达的负调控因子。mirna表现出组织特异性表达模式，其表达的变化可能有助于发病机制。本研究的目的是鉴定关节软骨细胞中表达的mirna，确定骨关节炎软骨的变化，并解决miR-140的功能。为了鉴定在软骨细胞中特异性表达的miRNA，我们使用miRNA微阵列和定量PCR对人关节软骨细胞与人间充质干细胞（MSC）进行了基因表达谱分析。miR-140的表达模式在颗粒培养和正常和骨关节炎膝关节的人关节软骨中的hMSC软骨分化过程中进行监测。我们测试了IL-1β对miR-140表达的影响。将双链（ds） miR-140转染软骨细胞，分析骨关节炎相关基因表达的变化。微阵列分析显示，miR-140在软骨细胞和间充质干细胞之间的表达差异最大。在MSC软骨培养过程中，miR-140的表达与Sox9和Col2a1平行增加。正常人关节软骨表达miR-140，在OA组织中明显降低。体外用IL-1β处理软骨细胞抑制miR-140的表达。用ds-miR-140转染软骨细胞可下调IL-1β诱导的ADAMTS-5表达，并恢复IL-1β依赖的聚集蛋白基因表达抑制。本研究表明，miR-140具有与软骨细胞分化相关的表达模式。miR-140在OA软骨中表达的降低以及对IL-1β的响应可能有助于OA特征的异常基因表达模式。
MicroRNAs (miRNAs) are a class of noncoding small RNAs that act as negative regulators of gene expression. The miRNAs exhibit tissue-specific expression patterns and changes in their expression may contribute to pathogenesis. The objectives of this study were to identify miRNAs expressed in articular chondrocytes, determine changes in osteoarthritic cartilage and address the function of miR-140. To identify miRNAs specifically expressed in chondrocytes, we performed gene expression profiling using miRNA microarrays and quantitative PCR with human articular chondrocytes compared to human mesenchymal stem cells (MSC). The expression pattern of miR-140 was monitored during chondrogenic differentiation of hMSC in pellet cultures and in human articular cartilage from normal and osteoarthritic knee joints. We tested effects of IL-1β on miR-140 expression. Double-strand (ds) miR-140 was transfected into chondrocytes to analyze changes in the expression of genes associated with osteoarthritis. Microarray analysis showed that miR-140 has the largest difference in expression between chondrocytes and MSC. During chondrogenesis cultures of MSC miR-140 expression increased in parallel with Sox9 and Col2a1. Normal human articular cartilage expressed miR-140 and this was significantly reduced in OA tissue. In vitro treatment of chondrocytes with IL-1β suppressed miR-140 expression. Transfection of chondrocytes with ds-miR-140 downregulated IL-1β-induced ADAMTS-5 expression and rescued the IL-1β –dependent repression of Aggrecan gene expression. This study shows that miR-140 has a chondrocyte differentiation-related expression pattern. The reduction in miR-140 expression in OA cartilage and in response to IL-1β may contribute to the abnormal gene expression pattern characteristic of OA.
登录
查看更多内容
影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
影响因子：
--
作者：
Grogan, Shawn P.;Olee, Tsaiwei;Hiraoka, Koji;Lotz, Martin K.
通讯作者：
Lotz, Martin K.
影响因子：
5
作者：
Goldring, M B
通讯作者：
Goldring, M B
影响因子：
--
作者：
Lawrence, Reva C.;Felson, David T.;Wolfe, Frederick
通讯作者：
Wolfe, Frederick
影响因子：
15.9
作者：
Little, Christopher B.;Meeker, Clare T.;Fosang, Amanda J.
通讯作者：
Fosang, Amanda J.