MicroRNA-223 is a key factor in osteoclast differentiation
MicroRNA-223 is a key factor in osteoclast differentiation
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DOI：
10.1002/jcb.21335
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发表时间：
2007-07-01
影响因子：
4
通讯作者：
Hruska, K. A.
中科院分区：
文献类型：
--
作者：
Sugatani, T.;Hruska, K. A.
MicroRNAs（miRNAs）是一类非编码RNA，在动植物中通过翻译抑制和信使RNA（mRNAs）降解来调控基因表达。尽管miRNAs参与了脊椎动物和无脊椎动物的发育和稳态事件，但miRNAs在骨代谢中的作用尚未被探索。在这里，我们发现microRNA-223（miR-223）在小鼠破骨细胞前体细胞系RAW264.7细胞中表达，并在破骨细胞分化中起关键作用。我们构建了miR-223短干扰RNA（siRNA）或前体miR-223（pre-miR-223）过表达逆转录病毒载体，并在稳定感染的RAW264.7细胞中建立了miR-223的siRNA敲除或pre-miR-223过表达。在miR-223敲低细胞以及对照细胞中观察到抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞。相比之下，与对照细胞相比，pre-miR-223过表达完全阻断TRAP阳性多核细胞的形成。本研究中未观察到凋亡细胞。我们的研究结果表明，miR-223在破骨细胞分化过程中起着至关重要的作用，miR-223可能是一个可行的治疗靶点，用于一系列具有过量破骨细胞活性的骨代谢疾病。
MicroRNAs (miRNAs) are a class of noncording RNAs that control gene expression by translational inhibition and messenger RNAs (mRNAs) degradation in plants and animals. Although miRNAs have been implicated in developmental and homeostatic events of vertebrates and invertebrates, the role of miRNAs in bone metabolism has not been explored. Here, we show that microRNA-223 (miR-223) is expressed in RAW264.7 cells, mouse osteoclast precursor cell lines, and plays a critical role in osteoclast differentiation. We constructed miR-223 short interfering RNA (siRNA) or precursor miR-223 (pre-miR-223) overexpression retroviral vectors, and established miR-223 knockdown by siRNA or pre-miR-223 overexpression in stably infected RAW264.7 cells. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were observed in miR-223 knockdown cells as well as control cells. In contrast, pre-miR-223 overexpression completely blocked TRAP-positive multinucleated cell formation compared with control cells. Apoptotic cells were not observed in this study. Our results indicate that miR-223 plays an essential role during osteoclast differentiation, and miR-223 might be a viable therapeutic target for a range of bone metabolic disorders with excess osteoclast activity.