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microRNA-155-3p attenuates intervertebral disc degeneration via inhibition of KDM3A and HIF1α

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Abstract

Objective

Intervertebral disc degeneration (IDD) is a key element resulting in low back pain, but the mechanisms underlying IDD remain largely unknown. The purpose of the study was to investigate the influence of microRNA-155-3p (miR-155-3p) on proliferation and autophagy of nucleus pulposus (NP) cells in IDD with the involvement of hypoxia-inducible factor 1 α (HIF1α)/histone lysine demethylase 3A (KDM3A) axis.

Methods

IDD NP tissues of patients with lumbar disc herniation and traumatic intervertebral disc NP tissues from patients with traumatic lumbar fracture were collected. Apoptosis in NP tissues was observed, and autophagy marker proteins in NP tissues were detected. NP cells in IDD were transfected with miR-155-3p mimic or KDM3A-siRNA to explore their roles in cell proliferation, autophagy and apoptosis. MiR-155-3p, KDM3A and HIF1α expression in NP tissues and cells were detected.

Results

Decreased miR-155-3p, and elevated HIF1α and KDM3A were presented in NP tissues and cells of IDD. Elevated miR-155-3p or silenced KDM3A promoted the proliferation and autophagy, and inhibited the apoptosis of NP cells of IDD. Moreover, elevated miR-155-3p decreased KDM3A and HIF1α expression, while silenced KDM3A decreased HIF1α expression in NP cells with IDD.

Conclusion

The study concludes that up-regulated miR-155-3p or silenced KDM3A promotes the proliferation, autophagy, and restrains the apoptosis of NP cells of IDD via inhibition of HIF1α, which may be a promising approach for the treatment of IDD.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

Funding

This work was supported by A research on personalized spinal three-dimensional printing intervertebral fusion cage in crenel lateral interbody fusion, office-level projects, 2019ZY1031, Key Scientific Research Projects on Chinese Medicine in Henan Province; Clinical application of personalized three-dimensional printing on external fixation of distal radius fractures, office-level projects, 1723001A-4, Scientific and Technological Development Projects in Luoyang City.

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Authors and Affiliations

  1. Spine Surgery, Luoyang Orthopedic Hospital of Henan Province, No. 100 Yongping Road, Henan, 450000, Zhengzhou, China

    Xianwei Zhou, Yufeng Liu, Di Zhang & Wenming Zhang

  2. Laboratory of Bone Tumor, Luoyang Orthopedic Hospital of Henan Province, Henan, 450000, Zhengzhou, China

    Jitian Li

  3. Department of Osteoarthrosis and Health Management Center, Luoyang Orthopedic Hospital of Henan Province, Henan, 450000, Zhengzhou, China

    Junyan Teng & Linyun Liu

Authors
  1. Xianwei Zhou
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  2. Jitian Li
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  3. Junyan Teng
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  4. Yufeng Liu
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  5. Di Zhang
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  7. Wenming Zhang
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Correspondence to Wenming Zhang.

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Zhou, X., Li, J., Teng, J. et al. microRNA-155-3p attenuates intervertebral disc degeneration via inhibition of KDM3A and HIF1α. Inflamm. Res. 70, 297–308 (2021). https://doi.org/10.1007/s00011-021-01434-5

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  • DOI: https://doi.org/10.1007/s00011-021-01434-5

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