THU0059 Plasma exosomal mir-92a are involved in the occurrence and development of bone destruction in ra patients by inhibiting apoptosis of fibroblast-like synoviocytes
Authors: Y. Xin, Z.S. Yang, X.Y. Fei, L.Y. Ke, J. Juan, F. Ting, Z.Z. Xu, Z. Gu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease that mainly affects joints. Bone erosion and bone destruction are the characteristic features of RA.<sup>1</sup> The mechanism of bone destruction is not fully understood at present. The decrease of apoptosis of human fibroblast-like synoviocytes (FLSs) originating from mesenchymal is involved in the occurrence and development of bone destruction in RA.<sup>2</sup> Exosomes are important mediators of biological information and play a part in the occurrence and development of various diseases including RA.<sup>3</sup> <h3>Objectives</h3> The aim of study was to find whether exosomes participate in the pathogenesis of bone destruction in RA. <h3>Methods</h3> plasma was collected from 10 healthy people and 20 RA patients. According to Sharp-van der Heijde score (SHS), patients were divided into two groups named bone destruction group and non bone destruction group. Exosomes were extracted by Total Exosome Isolation reagent and confirmed by transmission electron microscope and western blot. The internalisation of exosomes was detected by immunofluorescence. Normal FLSs were stimulated with exosomes. Flow cytometry was utilised to detect the alteration of cell cycle and apoptosis rate. The cell proliferation was determined by CCK-8 assay. Apotosis proteins (Bax, BCL-2 and caspase-3) were examined by western blot. The concentrations of TNF-α and IL-1 in the cell supernatants were measured by enzyme-linked immunosorbent assay (ELISA). High-throughput sequencing was used to detect the expression of miRNAs in exosomes. <h3>Results</h3> There is no difference between exosomes of normal people and RA patients in promoting cell proliferation. However, the exosomes of RA patients can prohibit the cell apoptosis and promote the release of TNF-α and IL-1 from FLSs more effectively. Of these two RA groups, the abilities of bone destruction group exosomes are higher. The expressions of Bcl-2 and caspase-3 in bone destruction group are also significantly higher than that in the non bone destruction group and the normal group. Inversely the expression of Bax in bone destruction group is lower. Additionally, exsomal miR-92a are significantly over expressioned in bone destruction group. <h3>Conclusions</h3> The study showed that exosomes in the serum of RA patients can prohibit the apoptosis of FLSs and enhance the secretion of inflammatory cytokines to promote bone destruction. Exosomes play an important role in the pathogenesis of RA. Exosomes can be used as a potential predictor for early bone destruction. <h3>References</h3> [1] Müller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol2005;1(2):102–10. [2] Lee DM, Kiener HP, Agarwal SK, Noss EH, Watts GF, Chisaka O, et al. Cadherin-11 in synovial lining formation and pathology in arthritis. ;Science 2007315 (5814):1006–10. [3] Schorey JS, Bhatnagar S. Exosome function: from tumour immunology to pathogen biology ;Traffic 20089 (6):871–81. <h3>Acknowledgements</h3> This work was supported by grants from Top Six Types of Talents Financial Assistance of Jiangsu Province Grant (BRA2016527), The Natural Science Foundation of China under Grant (81671616), The Natural Science Foundation of China under Grant (81471603). <h3>Disclosure of Interest</h3> None declared