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Review Open Access

Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)

  • Authors:
    • Luyan Wang
    • Ke Yang
    • Houjun Zhu
    • Dachuan Wang
    • Feng Wang
    • Xianfa Du
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, The Second Qilu Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Orthopaedics, Penglai People's Hospital, Yantai, Shandong 265600, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 111
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    Published online on: February 5, 2026
       https://doi.org/10.3892/mmr.2026.13821
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Abstract

Low back pain (LBP) is a leading cause of productivity loss worldwide and a major contributor to disability, imposing an economic burden on society. Intervertebral disc degeneration (IVDD) as a principal pathological driver of LBP remains a formidable therapeutic challenge, given that existing conservative and surgical interventions frequently fall short of achieving long‑term efficacy or halting disease progression. Advancements in molecular biology have revealed that circular RNAs (circRNAs) play a pivotal role in the intricate gene regulatory networks governing IVDD. The most extensively studied function of circRNAs is their ability to act as microRNA sponges. In addition, they participate in protein interactions, regulate gene transcription and serve as templates for protein translation. The present review provided a comprehensive overview of the current understanding of circRNA characteristics and functions, elucidated their involvement in IVDD pathogenesis and examined the therapeutic potential of emerging biomaterials for IVDD treatment. By consolidating existing research, the aim of this review was to offer theoretical foundations for innovative therapeutic strategies targeting IVDD.

View Figures

Figure 1

Pathophysiology of IVDD. The IVD,
composed of the NP, AF and nutrient-supplying CEP, undergoes
degeneration through multifactorial etiologies. Risk modulators
including lifestyle factors, biomechanical stress, socioeconomic
parameters and metabolic disorders collectively drive pathological
cascades. These stimuli induce cellular apoptosis, ECM degradation
and inflammatory mediator release, ultimately progressing to disc
structural failure. Advanced degeneration manifests as disc height
loss, annular rupture with NP herniation and nerve root
compression, establishing a direct mechanistic basis for chronic
low back pain. IVDD, intervertebral disc degeneration; NP, nucleus
pulposus; AF, annulus fibrosus; CEP, cartilaginous endplates; ECM,
extracellular matrix; MMP, matrix metalloproteinase; ADAMTs, A
disintegrin and MMP with thrombospondin motifs.

Figure 2

Function of circRNA. CircRNAs exert
multifaceted regulatory functions critical for cellular
homeostasis. Key mechanisms include: (A) miRNA sponging through
complementary base-pairing; (B) certain circRNAs can translate
proteins; (C) competitive splicing regulation that suppresses
canonical mRNA maturation; and (D) multimodal protein interactions,
functioning as scaffolds for ribonucleoprotein complexes,
modulating enzymatic activity through direct binding and serving as
molecular decoys for RBPs. circRNA, circular RNA; miRNA, microRNA;
RBPs, RNA-binding proteins.

Figure 3

Formation and classification of
circRNA. CircRNA biogenesis initiates with transcription-generated
precursor mRNA containing exon-intron sequences. While canonical
splicing produces linear mRNA through exon joining, circRNAs form
via back-splicing mechanisms. Three structural subtypes exist:
EcircRNA (exon-derived), eiciRNA (exon-intron hybrid) and ciRNA
(intron-retained), each exhibiting distinct functional properties.
circRNA, circular RNA; ecircRNA, exonic circRNA; eicircRNA,
exon-intron circRNA; ciRNA, circular intronic RNA.
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Copy and paste a formatted citation
Spandidos Publications style
Wang L, Yang K, Zhu H, Wang D, Wang F and Du X: <p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>. Mol Med Rep 33: 111, 2026.
APA
Wang, L., Yang, K., Zhu, H., Wang, D., Wang, F., & Du, X. (2026). <p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>. Molecular Medicine Reports, 33, 111. https://doi.org/10.3892/mmr.2026.13821
MLA
Wang, L., Yang, K., Zhu, H., Wang, D., Wang, F., Du, X."<p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>". Molecular Medicine Reports 33.4 (2026): 111.
Chicago
Wang, L., Yang, K., Zhu, H., Wang, D., Wang, F., Du, X."<p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>". Molecular Medicine Reports 33, no. 4 (2026): 111. https://doi.org/10.3892/mmr.2026.13821
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Yang K, Zhu H, Wang D, Wang F and Du X: <p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>. Mol Med Rep 33: 111, 2026.
APA
Wang, L., Yang, K., Zhu, H., Wang, D., Wang, F., & Du, X. (2026). <p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>. Molecular Medicine Reports, 33, 111. https://doi.org/10.3892/mmr.2026.13821
MLA
Wang, L., Yang, K., Zhu, H., Wang, D., Wang, F., Du, X."<p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>". Molecular Medicine Reports 33.4 (2026): 111.
Chicago
Wang, L., Yang, K., Zhu, H., Wang, D., Wang, F., Du, X."<p>Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review)</p>". Molecular Medicine Reports 33, no. 4 (2026): 111. https://doi.org/10.3892/mmr.2026.13821
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