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

• Elevation of TWIST1 in the later stages of S. aureus-induced osteomyelitis is associated with inflammatory microenvironments. • Depletion of TWIST1 impairs the bacterial phagocytosis/killing ability, accelerates apoptosis through mitochondrial dysfunction and exacerbates mitochondrial calcium overload in inflammatory microenvironments. • Inhibition of calcium overload significantly rescues macrophage apoptosis and enhances the antimicrobial ability in mice. 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. [ABSTRACT FROM AUTHOR]