作者
A. Pekáčová,Jiří Baloun,O. Šléglová,Olga Růžičková,Jiří Vencovský,Karel Pavelká,Ladislav Šenolt
摘要
Background: microRNAs (miRNAs) are small non-coding RNAs that can ignite the degradation of mRNAs or inhibit the protein translation and are therefore essential for several physiological and pathological functions. miRNAs can regulate up to 60 % of human mRNA, including genes related to cartilage development, homeostasis, and OA pathology. For example, miR-9 inhibits matrix metalloproteinase 13 or miR-140 expression level correlates with the disease progression of knee OA (Zhang et al.; Chao et al.). Under certain circumstances, miRNAs can be released into the body fluids and easily be detected in the blood samples. Therefore, miRNAs are hot candidates as biomarkers for early diagnosis or structural progression of OA. Objectives: The aim of this study was to evaluate circulating miRNAs in patients with hand osteoarthritis (HOA) and healthy individuals. Simultaneously, we studied specific miRNAs in order to differentiate between erosive and non-erosive subsets of the disease. Methods: Eight patients with HOA (erosive: n=4, 3 females, mean age=63.7±7 yrs; non-erosive: n=4, 3 females, mean age= 62.4±6 yrs) and 4 healthy controls (3 females, mean age=63.5±7 yrs) were included in this study. Firstly, Advance TaqMan low-density assay (TLDA) was performed for the purpose of miRNA high-throughput screening. Differently expressed miRNAs were further verified by real-time qPCR on the validation cohort in 31 patients with hand OA (19 females, mean age=66.2±7 yrs, erosive: n=9, non-erosive: n=10, healthy controls: n=12). Results: TLDA profiling displayed 346 circulating miRNAs in plasma of patients with HOA and healthy controls. We demonstrated 40 differently expressed circulating miRNAs in patients with HOA compared with healthy controls. Using a real-time qPCR, we verified increased expression levels of 10 circulating miRNAs in patients with HOA compared with healthy controls, e.g. miR-191-5p (3.4 fold), miR-151a-3p (3.4 fold) or miR-222-3p (2.4 fold). We did not find any specific miRNA, which could distinct erosive from a non-erosive subset of the disease. Conclusion: Extensive profiling of circulating miRNAs revealed several miRNAs that can be associated with HOA and can help to better understand OA pathogenesis. References: [1]Chao, Yu, et al. “Expression of MiR-140 and MiR-199 in Synovia and Its Correlation with the Progression of Knee Osteoarthritis.” Medical Science Monitor , vol. 26, 2020, pp. 1–6, doi:10.12659/MSM.918174. [2]Zhang, Hongxin, et al. “Downregulation of MicroRNA-9 Increases Matrix Metalloproteinase-13 Expression Levels and Facilitates Osteoarthritis Onset.” Molecular Medicine Reports , vol. 17, no. 3, 2018, pp. 3708–14, doi:10.3892/mmr.2017.8340. Acknowledgements: Supported by AZV NV18-01-00542, MHCR No. 023728 Disclosure of Interests: None declared