Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

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.

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions

“…To date, more than 2,000 functional miRNAs have been determined, and the expression of about 60% of the human gene is regulated by these miRNAs at the posttranscriptional level (Kloosterman and Plasterk, 2006;Silahtaroglu and Stenvang, 2010). Functionally, miRNAs can constitute the RNA-induced silencing complex and inhibit translation or induce degradation of mRNA through basepairing rules between the complementary sequences of miRNA and its target mRNAs (Gulyaeva and Kushlinskiy, 2016). It has been identified that dysregulated miRNA level is bound up with numerous physiological and pathological processes, including bone homeostasis (bone formation, resorption, remodeling, etc.)…”

Hub Genes and Key Pathways of Intervertebral Disc Degeneration: Bioinformatics Analysis and Validation

“…The anatomical structure of a complete intervertebral disc consists of the surrounding annulus fibrosus (AF), the central nucleus pulposus (NP), and the cartilage endplate (CEP) [ 18 ]. During IDD, inflammation, oxidative stress, apoptosis, senescence, and other pathological factors are involved.…”

NF‐κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration

“…They play important roles in maintaining the stability of the spine. 7 Current evidence shows that a series of factors, including inflammation, oxidative stress, mechanical stress, etc, promote the degradation of IVD extracellular matrix (ECM), leading to IVD dysfunction and structural destruction. [8][9][10] NF-κB signalling is very important for maintenance of IVD homeostasis.…”