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Long noncoding RNA lncAIS downregulation in mesenchymal stem cells is implicated in the pathogenesis of adolescent idiopathic scoliosis

Cell Death & Differentiation (2018) | Download Citation

Abstract

Adolescent idiopathic scoliosis (AIS) is a complex, three dimensional deformity of the spine that commonly occurs in pubescent girls. Abnormal osteogenic differentiation of mesenchymal stem cells (MSCs) is implicated in the pathogenesis of AIS. However, the biological roles of long noncoding RNAs (lncRNAs) in the regulation of osteogenic differentiation of MSCs are unknown. Through microarray analyses of bone marrow (BM) MSCs from healthy donors and AIS patients, we identified 1483 differentially expressed lncRNAs in AIS BM-MSCs. We defined a novel lncAIS (gene symbol: ENST00000453347) is dramatically downregulated in AIS BM-MSCs. In normal BM-MSCs, lncAIS interacts with NF90 to promote HOXD8 mRNA stability that enhances RUNX2 transcription in BM-MSCs, leading to osteogenic differentiation of normal BM-MSCs. By contrast, lncAIS downregualtion in AIS BM-MSCs cannot recruit NF90 and abrogates HOXD8 mRNA stability, which impedes RUNX2 transcription for osteogenic differentiation. Thereby lncAIS downregualtion in BM-MSCs suppresses osteogenic differentiation that is implicated in the pathogenesis of AIS.

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Acknowledgements

We thank Jing Li (Cnkingbio Company Ltd, Beijing, China) for technical support. We thank Peng Xue, Xiang Ding, Yan Teng, Yihui Xu, Junying Jia, Xudong Zhao and Xiaofei Guo for technical support. This work was supported by the National Natural Science Foundation of China (81272054, 81171673, 91640203), Beijing Talent Fund (2015000021223ZK27), Beijing Nova program Grant (2014A019), Beijing High-level Innovative Entrepreneurial Talent Fund, Beijing Natural Science Foundation (7181006). Peking Union Medical College Youth Fund, PUMC Nova program Grant of Chinese academy of medical sciences.

Author contributions

QZ, BY and SH designed and performed experiments; QZ and BY analyzed the data and wrote the paper; YD, RZ, JL, ZW, NL, YZ, HL, SW, and Y.Y. analyzed the data; JL, SL, and HZ performed some experiments; ZF organized, designed, and wrote the paper, and GQ and JZ initiated the study and analyzed the data.

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Author notes

  1. These authors contributed equally: Qianyu Zhuang, Buqing Ye, Shangyi Hui.

  2. These authors contributed equally: Zusen Fan, Guixing Qiu, Jianguo Zhang.

Affiliations

  1. Department of Orthopedics, Peking Union Medical College Hospital, Beijing, P.R. China

    • Qianyu Zhuang
    • , Zhihong Wu
    • , Yanbin Zhang
    • , Shengru Wang
    • , Yang Yang
    • , Shugang Li
    • , Hong Zhao
    • , Guixing Qiu
    •  & Jianguo Zhang
  2. CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    • Buqing Ye
    • , Ying Du
    •  & Zusen Fan
  3. Department of Anesthesiolgy, Peking Union Medical College Hospital, Beijing, China

    • Shangyi Hui
  4. Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    • Robert Chunhua Zhao
    • , Jing Li
    • , Na Li
    •  & Hongling Li

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The authors declare that they have no conflict of interest.

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Correspondence to Zusen Fan or Jianguo Zhang.

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DOI

https://doi.org/10.1038/s41418-018-0240-2