Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review
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REVIEW
Open Access
Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review Hao-Yu Guo1†, Ming-Ke Guo2†, Zhong-Yuan Wan3†, Fang Song4 and Hai-Qiang Wang5*
Abstract Intervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future. Keywords: Apoptosis, Cell proliferation, Extracellular matrix degeneration, Intervertebral disc degeneration, Inflammation, Noncoding-RNA, Nucleus pulposus cell
Background Intervertebral disc degeneration (IDD) is the most common cause of low-back pain, which affects over 70% of people at some points of their whole lifetime [1–3]. However, due to the poor understandings of the pathogenesis of the disorder, few treatment regimens have been put forward, and none of the current clinical interventions for IDD has been confirmed as efficient and radical treatment modalities [3–5]. Therefore, an in* Correspondence: [email protected]; [email protected] † Hao-Yu Guo, Ming-Ke Guo and Zhong-Yuan Wan contributed equally to this work. 5 Institute of Integrative Medicine, Shaanxi University of Chinese Medicine, Xixian Avenue, Xixian District, Shaanxi Province 712046, People’s Republic of China Full list of author information is available at the end of the article
depth investigation of the regulatory machinery of IDD is urgently needed in the present. Intervertebral disc (IVD) can be divided into three morphologically distinct regions, i.e., the sandwiched central nucleus pulposus (NP), peripheral annulus fibrosus (AF), and cranial or caudal cartilaginous endplate (CEP) (Fig. 1). During the process of IDD, the apoptosis of IVD cells is abnormally increased with the cells aberrantly clustering, dysregulation of extracellular matrix (
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