文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

环氧化酶-2抑制作为金黄色葡萄球菌骨髓炎骨质流失的治疗策略。

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

作者信息

Chen Yuhui, Li Chao, Jia Jishan, Jiang Yuhui, Zhang Ping, Cheng Caiyu, Zhang Guangyan, Gao Lang, Yang Xiang, Zhao Jiawei, Li Kaiqun, Yu Bin

机构信息

Division of Orthopedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, No. 1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China.

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.

出版信息

Mol Med. 2025 May 7;31(1):177. doi: 10.1186/s10020-025-01202-9.

DOI:10.1186/s10020-025-01202-9
PMID:40335904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12057237/
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.

摘要

金黄色葡萄球菌骨髓炎中的骨质流失给骨科治疗带来了严峻挑战，但慢性感染导致全身性骨质疏松的潜在机制尚不完全清楚。在本研究中，应用γ射线照射灭活的金黄色葡萄球菌（IKSA）来模拟炎症并探究其导致全身性骨质流失的机制。在本研究中，我们发现全身性应用IKSA通过增加破骨细胞和成骨细胞减少导致小鼠骨质流失。基于来自IKSA小鼠骨髓细胞的转录数据，确定了一种COX-2上调的免疫反应谱。在IKSA处理的小鼠中，骨髓免疫细胞如髓系来源的抑制细胞（MDSCs）、中性粒细胞和巨噬细胞中COX-2表达广泛上调。从机制上讲，COX-2刺激了MDSCs和中性粒细胞比例的增加以及骨髓免疫细胞的炎症反应，这可能调节骨代谢。重要的是，COX-2抑制剂塞来昔布可以挽救IKSA诱导的骨质流失，这可能是由于MDSCs、中性粒细胞和巨噬细胞中炎症基因表达的降低。令人兴奋的是，在金黄色葡萄球菌骨髓炎小鼠和患者的骨髓中COX-2表达也增加。这些发现表明抑制COX-2在对抗金黄色葡萄球菌骨髓炎骨质流失方面具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/974f71c18657/10020_2025_1202_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/dd90b8efa7e5/10020_2025_1202_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/9aa1a431e815/10020_2025_1202_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/81fcd1a8db05/10020_2025_1202_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/017e23c1c5a5/10020_2025_1202_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/6c10605a9d94/10020_2025_1202_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/2fc358dc7f8f/10020_2025_1202_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/219221ddcd7c/10020_2025_1202_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/974f71c18657/10020_2025_1202_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/dd90b8efa7e5/10020_2025_1202_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/9aa1a431e815/10020_2025_1202_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/81fcd1a8db05/10020_2025_1202_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/017e23c1c5a5/10020_2025_1202_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/6c10605a9d94/10020_2025_1202_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/2fc358dc7f8f/10020_2025_1202_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/219221ddcd7c/10020_2025_1202_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c336/12057237/974f71c18657/10020_2025_1202_Fig8_HTML.jpg

相似文献

[1]
COX-2 inhibition as a therapeutic strategy for bone loss in Staphylococcus aureus osteomyelitis.

Mol Med. 2025-5-7

[2]
G-CSF partially mediates bone loss induced by infection in mice.

Clin Sci (Lond). 2019-6-19

[3]
RANKL-mediated osteoclast formation is required for bone loss in a murine model of Staphylococcus aureus osteomyelitis.

Bone. 2024-10

[4]
MyD88 and IL-1R signaling drive antibacterial immunity and osteoclast-driven bone loss during Staphylococcus aureus osteomyelitis.

PLoS Pathog. 2019-4-12

[5]
Naringin exerts antibacterial and anti-inflammatory effects on mice with Staphylococcus aureus-induced osteomyelitis.

J Biochem Mol Toxicol. 2024-7

[6]
Age-related dysregulation of CXCL9/10 in monocytes is linked to impaired innate immune responses in a mouse model of Staphylococcus aureus osteomyelitis.

Cell Mol Life Sci. 2024-7-13

[7]
CHI3L1 regulation of inflammation and the effects on osteogenesis in a Staphylococcus aureus-induced murine model of osteomyelitis.

FEBS J. 2017-6

[8]
Osteoblasts produce monocyte chemoattractant protein-1 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue.

Bone. 2005-10

[9]
Granulocyte colony-stimulating factor mediates bone loss via the activation of IL-1β/JNK signaling pathway in murine Staphylococcus aureus-induced osteomyelitis.

Int Immunopharmacol. 2024-11-15

[10]
NEMO‑binding domain peptide ameliorates inflammatory bone destruction in a Staphylococcus aureus‑induced chronic osteomyelitis model.

Mol Med Rep. 2019-2-20

引用本文的文献

[1]
Mitochondrial metabolic regulation of macrophage polarization in osteomyelitis and other orthopedic disorders: mechanisms and therapeutic opportunities.

Front Cell Dev Biol. 2025-6-13

本文引用的文献

[1]
Design, classification, and adverse effects of NSAIDs: A review on recent advancements.

Bioorg Med Chem. 2024-10-1

[2]
Aspirin prevents estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis and promoting osteogenesis.

J Orthop Surg Res. 2023-3-22

[3]
Heat-Killed Induces Bone Mass Loss through Telomere Erosion.

Int J Mol Sci. 2023-2-6

[4]
The Role of COX-2 and PGE2 in the Regulation of Immunomodulation and Other Functions of Mesenchymal Stromal Cells.

Biomedicines. 2023-2-3

[5]
The osteoblast secretome in osteomyelitis.

Front Immunol. 2022

[6]
PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow.

Nat Commun. 2022-11-11

[7]
Neutrophil-Derived COX-2 has a Key Role during Inflammatory Hyperalgesia.

Inflammation. 2022-12

[8]
Isolation of human and mouse myeloid-derived suppressor cells for metabolic analysis.

STAR Protoc. 2022-6-17

[9]
Skeletal infections: microbial pathogenesis, immunity and clinical management.

Nat Rev Microbiol. 2022-7

[10]
N2-Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle.

Adv Sci (Weinh). 2021-10

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索