Circular RNA Interactions in Osteoarthritis Pathogenesis

Osteoarthritis (OA) is a degenerative joint disease characterised by progressive cartilage breakdown, subchondral bone remodelling and chronic inflammation. In recent years, circular RNAs (circRNAs) have emerged as pivotal regulators in OA pathogenesis. These covalently closed RNA molecules act as molecular sponges or scaffolds, sequestering microRNAs (miRNAs) or interacting with RNA-binding proteins to modulate gene expression. By influencing key signalling pathways—including NF-κB, MAPK and TGF-β—circRNAs control chondrocyte proliferation, apoptosis and extracellular matrix (ECM) homeostasis. They also respond to mechanical stress and oxidative insults, linking biomechanical overload and reactive oxygen species to cartilage degeneration. The growing elucidation of circRNA–miRNA–mRNA networks has revealed novel biomarkers of disease progression and potential therapeutic targets to preserve cartilage integrity and alleviate joint pain.

Research from Nature Portfolio

Recent studies have identified a circFNDC3B–miR-525-5p–HO-1 axis that defends chondrocytes against oxidative stress and ECM degradation. In vitro analyses demonstrated that circFNDC3B promotes chondrocyte proliferation, limits matrix-degrading enzyme induction and mitigates reactive oxygen species accumulation via upregulation of the antioxidant enzyme HO-1. Mechanistic investigations revealed that circFNDC3B modulates the NF-κB signalling cascade and directly binds miR-525-5p to relieve its inhibitory effect on HO-1 expression. In a rabbit osteoarthritis model, overexpression of circFNDC3B preserved cartilage structure and reduced synovial inflammation, highlighting its promise as a therapeutic agent to counteract oxidative and inflammatory stimuli in OA.

Circular RNA Interactions in Osteoarthritis Pathogenesis publication trend

The graph below shows the total number of articles in circular rna interactions in osteoarthritis pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Circular RNA (circRNA): A single-stranded RNA that forms a covalently closed loop, often regulating gene expression by binding microRNAs or proteins.

microRNA (miRNA): A small non-coding RNA that binds complementary sequences in messenger RNAs to repress translation or induce degradation.

Chondrocyte: The specialised cell type within cartilage responsible for synthesis and maintenance of the extracellular matrix.

Extracellular matrix (ECM): A complex network of proteins and polysaccharides secreted by cells that provides structural and biochemical support.

Competitive endogenous RNA (ceRNA): A transcript that regulates other RNAs by competing for shared miRNAs, thereby modulating gene expression networks.

Oxidative stress: A state in which the generation of reactive oxygen species exceeds the capacity of antioxidant defences, leading to cellular damage.

References

1. Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis. Frontiers in Immunology (2023).
2. CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis. Communications Biology (2023).
3. circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1. Annals of the Rheumatic Diseases (2021).