Effects of Ghrelin on the Apoptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocyte MH7A Cells

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Ghrelin is a circulating peptide hormone, which involved in promoting feeding and regulating energy metabolism in human and rodents. Abnormal synovial hyperplasia is the most important pathologic hallmark of rheumatoid arthritis (RA), which is characterised by tumor-like expansion. Existing studies indicated that there may exist some relation between the decreased ghrelin and the abnormally proliferating synovial cells in RA. Therefore, the aim of this study is to explore the apoptotic effects of ghrelin on MH7A synovial cells in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the effects of ghrelin on the viability of MH7A cells. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) and flow cytometry were used to test the apoptotic effects of ghrelin. At last, Western blot and real-time PCR were performed to explore the expression of caspases-8, -9, and -3 after the treatment of ghrelin. MTT experiments showed that ghrelin could inhibit viability of MH7A cells. The results of flow cytometry and TUNEL showed that ghrelin could induce apoptosis of MH7A synovial cells. Western blot showed that expression of cleaved-caspases-8, -9, and -3 were increased in ghrelin stimulation group compared with the control group, while expression of pro-caspases-8, -9, and -3 had no significant difference. In mRNA levels, ghrelin can decrease pro-caspases-8, -9, and -3 mRNA expression, which confirmed the results of protein levels. Then these apoptotic effects were significantly reversed by [D-Lys₃] GHRP-6 (ghrelin receptor antagonist). This study found that ghrelin can induce apoptosis of MH7A cells through caspase signaling pathways.