Biological roles and therapeutic potential of circular RNAs in osteoarthritis

Abstract

Osteoarthritis (OA) is a common and disabling joint disorder that is mainly characterized by cartilage degeneration and narrow joint spaces. The regulatory functions of non-coding RNAs (long non-coding RNAs, microRNAs [miRNAs], and circular RNAs [circRNAs]) in OA progression have attracted considerable attention, and the function of circular RNAs in the context of OA has been an increasingly popular research topic in the last 6 years. Recent studies have reported that various circRNAs can delay or aggravate diverse aspects of the OA process, including extracellular matrix formation, apoptosis, proliferation, inflammation, and autophagy, via circRNA/miRNA/ mRNA pathways. Thus, circRNAs and related pathways are potential therapeutic targets for OA. Our review provides comprehensive information about circRNAs, including their biogenesis, functions, and characteristics, and it reveals their critical roles in the pathogenesis of OA via a large regulatory network of sponges. Considering their regulatory functions and characteristics, we hypothesize that circRNAs not only can be transferred through bodily fluids to serve as diagnostic biomarkers, but they can also be released from mesenchymal stem cell-derived exosomes and delivered to OA chondrocytes acting as therapeutic circRNAs. Further investigations of the in-depth molecular mechanisms of action of circRNAs in OA are expected to provide effective and safe OA treatment strategies.

Genetic biomarkers in osteoarthritis: a quick overview

“…They are able to regulate gene expression by sponging RNA-binding proteins and miRNAs. Recent studies describe a series of functions of circRNAs in OA, including the modulation of metabolic homeostasis in cartilage matrix as well as their participation in inflammation, chondrocyte apoptosis, proliferation, and autophagy 26 , 27 . Examples of some recently discovered circRNAs as biomarkers in OA include the hsa_circ_0032132, which is significantly increased in the blood levels of patients with OA compared with healthy controls 28 , and the hsa_circ_0101873, hsa_circ_0104595, and hsa_circ_0101251, whose levels are significantly increased in the synovial fluid of patients with OA and even show a positive correlation with radiographic severity and WOMAC (Western Ontario and McMaster Universities Arthritis Index) score 29 .…”

Circular RNA hsa_circ_0005567 overexpression promotes M2 type macrophage polarization through miR-492/SOCS2 axis to inhibit osteoarthritis progression

“…Circular RNAs (circRNAs) are noncoding RNA molecules characterized by covalent closed loops free of 3ʹ and 5ʹ ends [ 10 ]. An increasing number of researches have suggested that novel circRNAs play various roles in osteoarthritis progression [ 11 ], such as CircCDH13 [ 12 ], circCSNK1G1 [ 13 ], circ_0128846 [ 14 ], etc. Has_circ_0005567 was first reported as osteoarthritis-related circRNA [ 15 ].…”

Novel circular RNA circATRNL1 accelerates the osteosarcoma aerobic glycolysis through targeting miR-409-3p/LDHA

“…In the constant exploration for osteosarcoma pathogenesis, increasing number of circRNAs have been discovered and their functions attract more and more attention [ 16 , 17 ]. In terms of biogenesis, circRNAs were generated from certain gene via back-splicing, which is a special splicing manner [ 18 , 19 ]. Circular RNAs are a novel class of non-coding RNAs that are regulating more and more pathophysiological process in the regulation of osteosarcoma.…”