Chinese Journal of Tissue Engineering Research ›› 2016, Vol. 20 ›› Issue (7): 940-946.doi: 10.3969/j.issn.2095-4344.2016.07.004

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Differential expression of microRNAs in the intervertebral disc of hypoxia-inducible factor-1alpha deficient mice 

Meng Xiang-chao, Liu Zhuo-chao, Wang Jun, Zhou Qi, Qi Jin, Zhang Xing-kai   

  1. Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traumatology and Orthopaedics, Shanghai 200025, China
  • Received:2015-08-07 Online:2016-02-12 Published:2016-02-12
  • Contact: Zhang Xing-kai, M.D., Associate chief physician, Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traumatology and Orthopaedics, Shanghai 200025, China
  • About author:Meng Xiang-chao, Studying for master’s degree, Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traumatology and Orthopaedics, Shanghai 200025, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81071502; the Scientific Research Project of Shanghai Science and Technology Commission, No. 15ZR1437600

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Abstract:

BACKGROUND: It is confirmed that the absence of hypoxia-inducible factor-1α (HIF-1α) accelerates the degenerative process in the intervertebral discs, and microRNAs have an important role in degeneration of the intervertebral discs.
OBJECTIVE: To evaluate the changes of microRNAs in the intervertebral discs of HIF-1α-deficient (HIF-1α-/-) mice which may mediate the signaling pathway of HIF-1α in the intervertebral discs.
METHODS: As previously reported, HIF-1α-/- mice were established. HIF-1α-/- mice and HIF-1αflox/flox mice (control mice) aged 4 weeks were used. MRI and histological staining were used to evaluate the degeneration of the intervertebral discs. Total RNAs were extracted from the intervertebral discs tissues by Trizol, and the differential expression profile of microRNAs was harvested by significance analysis of microarrays and Cluster, based on microarray screening. Real-time quantitative reverse transcription-PCR was applied to verify the reliability of microRNA array results.
RESULTS AND CONCLUSION: The number of nucleus pulposus cells in the intervertebral discs of HIF-1α-/- mice was decreased, the cells presented with small size and the color deepened in the cytoplasm. Finally, differential expression profile of microRNAs (n=10) was obtained, seven of which were upregulated and three were downregulated. In conclusion, the loss of HIF-1α may cause the imbalance of some important miRNAs, which may result in a large amount of dead nuclear pulposus cells and mediate disc degeneration in HIF-1α-/- mice.