Identification of exosomal mRNA, lncRNA and circRNA signatures in an osteoarthritis synovial fluid-exosomal study.

Aims: Osteoarthritis (OA) is a common degenerative disease that is pathologically characterized by destruction of the joint matrix and reduction of articular chondrocytes, resulting in joint deformity and motor dysfunction. However, the molecular mechanisms governing this pathology have not been elucidated to date.

Methods: In this study, we determined the expression levels of lncRNAs, circRNAs, and mRNAs extracted from synovial exosomes of OA and control patients. A network of circRNA/lncRNA-miRNA-mRNA interactions was established using MiRanda and TargetScan software to explore OA pathogenesis. The exosomal lncRNA, circRNA and mRNA expression profiles of the OA and control groups were analysed using LC human competing endogenous RNA (ceRNA) microarrays. The differentially expressed genes were analysed to determine their potential roles in the pathogenesis of OA by bioinformatic analysis.

Results: There were 52 mRNAs, 196 lncRNAs and 98 circRNAs differentially expressed in synovial exosomes between osteoarthritis synovial and the control group. The final ceRNA network of lncRNAs and circRNAs exhibited a complex interaction between ncRNA and mRNA related to OA pathological mechanisms. An intersection analysis of the ceRNA network showed that 22 miRNAs, 45 lncRNAs, and 34 circRNAs enriched in the PI3K/Akt and autophagy pathways correlated with 7 mRNAs and may play important roles in OA pathological mechanisms.

Conclusion: Our work analysed mRNA/lncRNA/circRNA expression and displayed the ceRNA network of lncRNAs and circRNAs to profile the pathogenesis of OA in synovial exosomes. The results of this study may help to elucidate the pathogenesis of OA and may provide important references for further research attempting to identify more effective targets for the diagnosis and therapy of OA.