Granulocyte colony-stimulating factor mediates bone loss via the activation of IL-1β/JNK signaling pathway in murine Staphylococcus aureus-induced osteomyelitis

• Published in: International immunopharmacology Vol. 141; p. 112959
• Main Authors: Song, Mingrui, Deng, Mingye, Peng, Ziyue, Dai, Fangfang, Wang, Yutian, Shu, Wen, Zhou, Xuyou, Zhang, Jinye, Hou, Yilong, Yu, Bin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.11.2024
• Subjects: BMSC senescence; Bone loss; G-CSF; IL-1β; JNK; Osteomyelitis; TV; Tb. N; BMSC senescence; BMSC; Tb. Th; JNK; Tb. Sp; IL-1β; G-CSF; NAb; BMNs; Osteomyelitis; BV; Bone loss
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112959

[Display omitted] •G-CSF indirectly mediated BMSC senescence in mice after S. aureus infection.•G-CSF elevated both local and systemic IL-1β levels after S. aureus infection.•IL-1β directly mediated BMSC senescence by JNK/P53 and JNK/BCL2 pathways.•Blocking IL-1β rescued BMSC senescence and bone loss in a murine model of S. aureus osteomyelitis.•Our study provides new targets for prevention and treatment of bone loss caused by S. aureus infection. Staphylococcus aureus (S. aureus)-induced bone loss is a significant challenge in the treatment of osteomyelitis. Our previous study was the first to confirm that granulocyte colony-stimulating factor (G-CSF) mediates S. aureus-induced bone loss. However, the underlying mechanism remains unknown. The objective of this study was to elucidate this. We found G-CSF mediated BMSC senescence and increased IL-1β concentration of serum and bone marrow in mice after S. aureus infection. Furthermore, we demonstrated that G-CSF promoted the expression of IL1b in murine bone marrow–derived neutrophils. Notably, we identified that IL-1β mediated BMSC (bone marrow mesenchymal stromal cell) senescence in mice after S. aureus infection. Importantly, IL-1β neutralizing antibody effectively alleviated BMSC senescence and bone loss caused by S. aureus infection in mice. In terms of molecular mechanism, we found IL-1β induced BMSC senescence by JNK/P53 and JNK/BCL2 pathways. Collectively, G-CSF promotes IL-1β production which induces BMSC senescence via JNK/P53 and JNK/BCL2 pathways, leading to S. aureus-induced bone loss. This study identified novel targets for preventing and treating S. aureus-induced bone loss in osteomyelitis.