Signal cascade after cyclic compressive load in human synovial fibroblasts cultured on three-dimensional collagen constructs.

Research Project

Project/Area Number	25462370
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Orthopaedic surgery
Research Institution	Osaka University
Principal Investigator	YONETANI YASUKAZU 大阪大学, 医学(系)研究科(研究院), 助教 (80642090)
Co-Investigator(Kenkyū-buntansha)	NAKATA Ken 大阪大学, 医学系研究科, 教授 (00283747) 前達雄大阪大学, 医学(系)研究科(研究院), 講師 (10569734)
Co-Investigator(Renkei-kenkyūsha)	MAE Tatsuo 大阪大学, 医学系研究科, 講師 (10569734)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000) Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	力学刺激応答 / 滑膜細部 / インターロイキン６ / インターロイキン１ / 炎症反応 / 力学刺激 / 滑膜細胞 / 三次元培養組織 / シグナルカズケード / IL6 / PGE2 / 変形性関節症 / 炎症性変化
Outline of Final Research Achievements	Human synovial fibroblasts were cultured on collagen scaffolds to produce three-dimensional constructs. A cyclic compressive loading of 40 kPa at 0.5 Hz was applied to the constructs. The concentrations of PGE2, IL-1 and IL-6 in the loaded samples were significantly higher than those of unloaded samples. After the administration of a IL6 or IL1 selective inhibitor, the increased concentration of PGE2 by cyclic compressive loading was impeded. Although administration of IL6 without loading did not upregulate PGE2 production, promotion of PGE2 was occurred after IL6 stimulation with higher concentration of soluble IL6 receptor. However, the amount of PGE2 was less than that of PGE2 after IL1 stimulation. These data indicated that cyclic compressive loading stimulates IL1 pathway and IL6 pathway including not only production of IL6 but also the function of IL6 receptor.