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Ann Rheum Dis. 2018 May;77(5):770-779. doi: 10.1136/annrheumdis-2017-212056. Epub 2018 Jan 17.

Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein.

Author information

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
Department of Neurosurgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
3
Department of Orthopedics, Clinical Medical College of Yangzhou University, Jiangsu Subei People's Hospital, Yangzhou, China.
4
Department of Orthopedics, The General Hospital of Chinese People's Liberation Army, Beijing, China.
5
Department of Toxicity Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
#
Contributed equally

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.

KEYWORDS:

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

PMID:
29343508
PMCID:
PMC5909753
DOI:
10.1136/annrheumdis-2017-212056
[Indexed for MEDLINE]
Free PMC Article

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