Characteristics of plasma exosomal RNA profile in obesity-related knee osteoarthritis

Abstract

Abstract Background: As the most important risk factors of knee osteoarthritis (OA), obesity is closely related to the clinical symptoms and OA progression of patients. The purpose of this study was to explore the characteristics of exosomal RNAs in plasma of knee OA patients with obesity and discussed their potential diagnostic and therapeutic value in obese knee OA. Methods: The 101 participants with knee OA patients were divided into three groups according to BMI class. The corresponding clinical information was recorded and the correlation with obesity was analyzed. Next, we extracted the plasma exosomes from three OA patients with obesity (BMI≥30kg/m2) and three OA patients without obesity (BMI 18.5-24kg/m2). Then, quantitative sequencing of the whole transcriptome exosomal RNAs, including mRNAs, lncRNAs and circRNAs, was performed and the differential expression of the exosomal RNAs were analyzed. At last, the function of differential RNAs in plasma exosomes between the two groups were discussed via GO enrichment, KEGG pathways and interaction Analysis. Results: There was a negative relationship between BMI and HSS (Hospital for special surgery) score and a positive relationship between BMI and WOMAC (The Western Ontario and McMaster Universities Osteoarthritis) index in 101 participants with knee OA. There were 334 mRNAs and 29 lncRNAs showing significant differential expression between obesity OA group and non-obesity OA group, including 189 up-regulated mRNAs, 145 down-regulated mRNAs, 15 up-regulated lncRNAs and 14 down-regulated lncRNAs. Signal pathway analysis showed that metabolism-related changes including metabolism and organismal system, fatty acid metabolism, positive regulation of fatty acid oxidation, adipocytokine signaling pathway, insulin resistance were enriched in obesity-related OA group. Furthermore, 7 differentially expressed lncRNAs related to lipid metabolism process were screened out, including lnc-TAL1-3-2, NONHSAT209148.1, lnc-DLEU2, Inc00969, lnc-CABP4-2, lnc-CHD1L-5 and lnc-ERICH1-19. However, there was no differential expression of cirRNAs between two groups. Conclusion: Knee OA patients with obesity had more serious clinical symptoms and signs. Compared to the control group, there was obviously differential expression of mRNAs and lncRNAs in plasma exosomes of knee OA patients with obesity. The differential mRNAs and lncRNAs in plasma exosomes may potentially affect synovial inflammation of joint and participate in the pathological injury of OA. Our data suggested that plasma exosomal RNA may be a potential diagnostic and intervention target for OA patients with obesity in the future.