2. Academic Validation
  3. COX-2 inhibition as a therapeutic strategy for bone loss in Staphylococcus aureus osteomyelitis

COX-2 inhibition as a therapeutic strategy for bone loss in Staphylococcus aureus osteomyelitis

  • Mol Med. 2025 May 7;31(1):177. doi: 10.1186/s10020-025-01202-9.
Yuhui Chen # 1 2,  Chao Li # 1 2,  Jishan Jia # 1 2,  Yuhui Jiang 1 2,  Ping Zhang 1 2,  Caiyu Cheng 1 2,  Guangyan Zhang 1 2,  Lang Gao 3,  Xiang Yang 3,  Jiawei Zhao 3,  Kaiqun Li 4 5,  Bin Yu 6 7
Affiliations

Affiliations

  • 1 Division of Orthopedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China.
  • 2 Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China.
  • 3 Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China.
  • 4 Division of Orthopedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China. likaiqun11@163.com.
  • 5 Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China. likaiqun11@163.com.
  • 6 Division of Orthopedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China. yubin@smu.edu.cn.
  • 7 Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China. yubin@smu.edu.cn.
  • # Contributed equally.
PMID: 40335904 DOI: 10.1186/s10020-025-01202-9
Abstract

Bone loss in Staphylococcus aureus (S. aureus) osteomyelitis poses a serious challenge to orthopedic treatment, but the underlying mechanism of systemic osteoporosis caused by chronic Infection is not completely clear. In this study, γ-irradiation-killed S. aureus (IKSA) was applied to simulate the inflammation and explore the mechanism of systemic bone loss caused by it. In this study, we found that the systemic application of IKSA caused bone loss in mice through increasing osteoclasts and decreasing osteoblasts. An immune response profile with up-regulated COX-2 is identified based on our transcriptional data from IKSA mice bone marrow cells. COX-2 expression is widely up-regulated in bone marrow immune cells, such as myeloid-derived suppressor cells (MDSCs), neutrophils and macrophages in the IKSA-treated mice. Mechanistically, COX-2 stimulated the increasing proportion of MDSCs and neutrophils and the inflammatory response of the bone marrow immune cells, that may regulate bone metabolism. Importantly, COX-2 Inhibitor, celecoxib could rescue the bone loss induced by IKSA, which may reason from decrease of inflammatory gene expression in MDSCs, neutrophils and macrophages. Excitingly, COX-2 expression is also increased in bone marrow from mice and patients with S. aureus osteomyelitis. These findings suggested a therapeutic potential for inhibiting COX-2 in combating bone loss in S. aureus osteomyelitis.

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