A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation
A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation
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一种新型长非编码 RNA AK016739 抑制成骨细胞分化和骨形成
DOI：
10.1002/jcp.27815
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Qian, Airong
中科院分区：
文献类型：
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作者：
Yin, Chong;Tian, Ye;Qian, Airong
研究显示绝经后骨质疏松症的发病率在50%以上是中老年女性，然而现有的治疗方法效果并不理想。新的证据证明长链非编码RNA（lncRNA）与多种生理和病理过程相关，包括发育、癌变和成骨。然而，有关lncRNA调节骨形成的报道相对有限。在本研究中，我们通过mRNA/lncRNA微阵列结合基因共表达分析来筛选成骨lncRNA。在体外和体内评估了筛选的lncRNA的生物学功能。还评估了 lncRNA 对成骨转录因子的影响。我们鉴定了 AK016739，它与成骨分化相关并在小鼠骨骼组织中富集。骨源间充质干细胞中AK016739的表达水平随着年龄的增长而增加，且与成骨分化标志基因呈负相关。实验表明，AK016739 抑制成骨细胞分化，并且通过其小干扰 RNA 体内抑制 AK016739 将挽救卵巢切除骨质疏松小鼠模型的骨形成。此外，AK016739 抑制成骨转录因子的表达水平和活性。这种新鉴定的lncRNA AK016739揭示了成骨分化的新机制，为骨骼疾病的治疗提供了新的靶点。
The incidence of postmenopausal osteoporosis research 50% in middle-aged and older women, however, effects of existing therapy are not ideal. Emerging evidence have proved that long noncoding RNAs (lncRNAs) was correlated with multiple physiological and pathology processes including development, carcinogenesis, and osteogenesis. However, reports on lncRNAs regulating bone formation were relatively limited. In this study, we screened osteogenic lncRNAs through mRNA/lncRNA microarray combined with gene coexpression analysis. The biological function of the screened lncRNA was assessed both in vitro and in vivo. The effects of the lncRNA on osteogenic transcription factors were also evaluated. We identified AK016739, which was correlated with osteogenic differentiation and enriched in skeletal tissues of mice. The expression levels of AK016739 in bone-derived mesenchymal stem cells were increased with age and negatively correlated with osteogenic differentiation marker genes. Experiments showed that AK016739 inhibited osteoblast differentiation, and in vivo inhibition of AK016739 by its small interfering RNA would rescue bone formation in ovariectomized osteoporosis mice model. In addition, AK016739 suppressed both expression levels and activities of osteogenic transcription factors. This newly identified lncRNA AK016739 has revealed a new mechanism of osteogenic differentiation and provided new targets for treatment of skeletal disorders.