Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway
作者机构：Department of OrthopedicsThe First Affiliated Hospital of Soochow UniversityOrthopedic InstituteMedical CollegeSoochow University188 Shizi RoadSuzhouJiangsu215006PR China Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology199 Renai RoadSuzhou215123PR China
出 版 物：《Bioactive Materials》 (生物活性材料（英文）)
年 卷 期：2020年第5卷第4期
页 面：880-890页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 081702[工学-化学工艺] 07[理学] 08[工学] 0817[工学-化学工程与技术] 071009[理学-细胞生物学] 09[农学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种]
基 金：supported by the National Natural Science Foundation of China(81772312,891972059,81772358) Research and Development of Biomedical Materials and Substitution of Tissue and Organ Repair under the National Key R&D Program(2016YFC1101502) the Natural Science Foundation of Jiangsu Province(BK2019668,BK20151210) Jiangsu Provincial Clinical Orthopedic Center,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
主 题：Substrate stiffness Macrophage polarization NF-κB signaling pathway
摘 要：The stiffness of the extracellular matrix(ECM)plays an important role in regulating the cellular ***,the mechanical characteristics of ECM affecting cell differentiation are still under ***,we aimed to study the effect of ECM substrate stiffness on macrophage *** prepared polyacrylamide hydrogels with different substrate stiffness,*** the hydrogels were confirmed to have a good biocompatibility,the bone marrow-derived macrophages(BMMs)from mice were incubated on the *** simulated by the low substrate stiffness,BMMs displayed an enhanced expression of CD86 on the cell surface and production of reactive oxygen species(ROS)in cells,and secreted more IL-1βand TNF-αin the *** the contrary,stressed by the medium stiffness,BMMs expressed more CD206,produced less ROS,and secreted more IL-4 and TGF-β.In vivo study by delivered the hydrogels subcutaneously in mice,more CD68+CD86+cells around the hydrogels with the low substrate stiffness were observed while more CD68+CD206+cells near by the middle stiffness *** addition,the expressions of NIK,phosphorylated p65(pi-p65)and phosphorylated IκB(pi-IκB)were significantly increased after stimulation with low stiffness in *** together,these findings demonstrated that substrate stiffness could affect macrophages *** substrate stiffness promoted BMMs to shift to classically activated macrophages(M1)and the middle one to alternatively activated macrophages(M2),through modulating ROS-initiated NF-κB ***,we anticipated ECM-based substrate stiffness with immune modulation would be under consideration in the clinical applications if necessary.
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