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Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein
  1. Xiaofei Cheng1,2,
  2. Liang Zhang3,
  3. Kai Zhang1,
  4. Guoying Zhang4,
  5. Ying Hu5,
  6. Xiaojiang Sun1,
  7. Changqing Zhao1,
  8. Hua Li1,
  9. Yan Michael Li2,
  10. Jie Zhao1
  1. 1 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  2. 2 Department of Neurosurgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  3. 3 Department of Orthopedics, Clinical Medical College of Yangzhou University, Jiangsu Subei People’s Hospital, Yangzhou, China
  4. 4 Department of Orthopedics, The General Hospital of Chinese People’s Liberation Army, Beijing, China
  5. 5 Department of Toxicity Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
  1. Correspondence to Dr Jie Zhao, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, China; profzhaoj{at}sina.com

Abstract

Objectives Circular RNAs (circRNAs) have been proven to function as competing endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression of miRNA target mRNAs. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of intervertebral disc degeneration (IVDD).

Methods The role and mechanism of a circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and degenerative NP tissues from patients and rat models. The interaction between circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of-apoptosis protein (XIAP), was examined.

Results The decreased expression of XIAP in the inflammatory cytokines-treated NP cells and the degenerative NP tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix. miR-200c regulated NP cell viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of miR-200c and functioned in NP cells through targeting miR-200c and XIAP. Intradiscal injection of circVMA21 alleviated IVDD in the rat model.

Conclusions CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and imbalance between anabolism and catabolism of extracellular matrix through miR-200c-XIAP pathway. It provides a potentially effective therapeutic strategy for IVDD.

  • cytokines
  • osteoarthritis
  • tnf-alpha
  • low back pain
  • inflammation

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Footnotes

  • XC and LZ contributed equally.

  • Handling editor Tore K Kvien

  • Contributors XC and JZ designed the experiments. XC, LZ, KZ, GZ, YH and XS performed the experiments and acquired the data. XC, LZ, CZ and HL analysed the data. XC, YML and JZ supervised the project and wrote the manuscript.

  • Funding This work was supported by grants from the National Natural Science Foundation of China (81572168, 81401830), and the Industry-Academy-Research Cooperation Project of Shanghai Science and Technology Committee (13DZ1940504, 13DZ1940505), the Natural Science Foundation of Shanghai, the Department Integration Foundation (160065), and the Fundamental Research Program Funding of the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethics Committee of Shanghai Ninth People’s Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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