Emerging role of lncRNAs in osteoarthritis: An updated review

Abstract

Osteoarthritis (OA) is a prevalent joint disease, which is associated with progressive articular cartilage loss, synovial inflammation, subchondral sclerosis and meniscus injury. The molecular mechanism underlying OA pathogenesis is multifactorial. Long non-coding RNAs (lncRNAs) are non-protein coding RNAs with length more than 200 nucleotides. They have various functions such as modulating transcription and protein activity, as well as forming endogenous small interfering RNAs (siRNAs) and microRNA (miRNA) sponges. Emerging evidence suggests that lncRNAs might be involved in the pathogenesis of OA which opens up a new avenue for the development of new biomarkers and therapeutic strategies. The purpose of this review is to summarize the current clinical and basic experiments related to lncRNAs and OA with a focus on the extensively studied H19, GAS5, MALAT1, XIST and HOTAIR. The potential translational value of these lncRNAs as therapeutic targets for OA is also discussed.

Keywords: biomarkers; long non-coding RNA; osteoarthritis; pathogenesis; therapeutic strategies.

Figure 1

Biogenesis and function of lncRNAs. Classification of lncRNAs into five classes: sense lncRNAs, intronic lncRNAs, lincRNAs, antisense lncRNAs and bidirectional lncRNAs, based upon their genomic locations and transcription. LncRNAs regulate the expression of genes in the cytoplasm by interacting directly with microRNAs (miRNAs) or proteins, and stabilizing mRNA transcripts. Noncoding transcripts in the nucleus are known to regulate gene expression at the level of chromatin modification, transcription and post-transcriptional processing. In addition, lncRNAs are considered as biomarkers or participant in tissue crosstalk by entering the bloodstream directly, or bound to carrier proteins, even incorporated into extracellular vesicles which can be further released into bloodstream.

Figure 2

Potential delivery strategies for lncRNA H19 is proposed in OA treatment. (A) Nanotechnology and lncRNA-loaded exosomes could overcome the low efficiency of in vivo transgene lncRNA transfection, which would be applicable for widespread clinical application of gene therapy targeting lncRNAs. (B) Various transgene technologies may benefit lncRNA overexpression or downregulations in vivo studies, which opened a new door in studying the delivery of genetic material for OA treatment.