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

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

  • Int Immunopharmacol. 2024 Nov 15:141:112959. doi: 10.1016/j.intimp.2024.112959.
Mingrui Song 1,  Mingye Deng 1,  Ziyue Peng 1,  Fangfang Dai 2,  Yutian Wang 1,  Wen Shu 3,  Xuyou Zhou 1,  Jinye Zhang 1,  Yilong Hou 4,  Bin Yu 5
Affiliations

Affiliations

  • 1 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Huiqiao Medical Center, Nanfang Hospital of Southern Medical University, Guangzhou, China.
  • 3 Department of Trauma Orthopedics, Liuzhou People's Hospital, Liuzhou, Guangxi, China.
  • 4 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: xiaoyihou128@smu.edu.cn.
  • 5 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: yubin@smu.edu.cn.
PMID: 39163688 DOI: 10.1016/j.intimp.2024.112959
Abstract

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.

Keywords

BMSC senescence; Bone loss; G-CSF; IL-1β; JNK; Osteomyelitis.

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