TWIST1 rescue calcium overload and apoptosis induced by inflammatory microenvironment in S. aureus-induced osteomyelitis

作者：Yutian Wang, Guandong Dai, Zexin Lin, Caiyu Cheng, Xuyou Zhou, Mingrui Song, Peng Chen, Sushuang Ma, Yanjun Hu, Guanqiao Liu, Bin Yu · 发表于：International Immunopharmacology · 年份：2023 · DOI：10.1016/j.intimp.2023.110153 · 被引用次数：9 · 研究领域：Immune Response and Inflammation、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Orthopedic Infections and Treatments

Currently, there is no effective therapy for Staphylococcus aureus-induced osteomyelitis. It is widely recognized that the inflammatory microenvironment around abscess plays an essential role in protracting the course of S. aureus-induced osteomyelitis. In this study, we found TWIST1 was highly expressed in macrophages around abscesses but less related to local S. aureus in the later stages of Staphylococcus aureus-infected osteomyelitis. Mouse bone marrow macrophages show apoptosis and elevated TWIST1 expression when treated with the inflammatory medium. Knockdown of TWIST1 induced macrophage apoptosis, impaired the bacteria phagocytosis/killing abilities, and promoted cell apoptosis markers expression in inflammatory microenvironment stimulation. Furthermore, inflammatory microenvironments were responsible for inducing calcium overload in macrophage mitochondrial while calcium overload inhibition significantly rescued macrophage apoptosis, bacteria phagocytosis/killing abilities and improved the mice's antimicrobial ability. Our findings indicated that TWIST1 is a crucial molecule that protects macrophages from calcium overload induced by inflammatory microenvironments.