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. 2018 Jul 27;9:1714. doi: 10.3389/fimmu.2018.01714

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Copyright © 2018 Shi, Wang, Xiao, Wang, Qiu, Lao, Yu, Li, Zhang, Ye, Liang, Yang, Chen and Xu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Attenuation of the severity of disease in rats with collagen-induced arthritis (CIA) by local joint depletion of glycogen synthase 1 (GYS1) or intraperitoneal administration of an AMP-activated protein kinase (AMPK) agonist. The CIA model was generated in SD rats. (A,B) Effect of local joint depletion of GYS1 on the articular index [upper panel of (B)] and paw swelling [change in volume, lower panel of (B)] in rats with CIA. The values in (B) are the mean ± SD from eight rats untreated or treated with GYS1 or scramble interference lentivirus in local joints. (C) Representative images of histological findings [hematoxylin and eosin (H&E), 200×], GYS1 expression (immunohistochemical staining, 200×), and glycogen [periodic acid Schiff (PAS) staining, 200×] in joint synovial tissue (ST) from CIA rats. (D) The scores (mean ± SD) for synovial infiltration (syno), cartilage erosion (cart), and bone loss (bone). (E) Semi-quantitative chart (mean ± SD) of PAS staining for ST sections from CIA rats. (F,G) Effect of the AMPK agonist AICAR on the severity of disease in rats with CIA. CIA rats were treated with intraperitoneal injection of AICAR (25 mg/kg/day, once daily) or 5% DMSO (vehicle, once daily) for a total of 14 days. The articular index [left panel of (G)] and paw swelling [change in volume, right panel of (G)] in rats with CIA are shown. (H) Representative H&E staining images and (I) the scores (mean ± SD) for synovial infiltration (syno), cartilage erosion (cart), and bone loss (bone) for joint ST from CIA rats. Original magnification 200×. *P < 0.05, **P < 0.01 vs. scramble or vehicle. (J) A model for the role of GYS1 in regulation of synovial inflammation in patients with rheumatoid arthritis.