{"title":"COX-2抑制作为治疗金黄色葡萄球菌骨髓炎骨质流失的策略。","authors":"Yuhui Chen, Chao Li, Jishan Jia, Yuhui Jiang, Ping Zhang, Caiyu Cheng, Guangyan Zhang, Lang Gao, Xiang Yang, Jiawei Zhao, Kaiqun Li, Bin Yu","doi":"10.1186/s10020-025-01202-9","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"177"},"PeriodicalIF":6.0000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057237/pdf/","citationCount":"0","resultStr":"{\"title\":\"COX-2 inhibition as a therapeutic strategy for bone loss in Staphylococcus aureus osteomyelitis.\",\"authors\":\"Yuhui Chen, Chao Li, Jishan Jia, Yuhui Jiang, Ping Zhang, Caiyu Cheng, Guangyan Zhang, Lang Gao, Xiang Yang, Jiawei Zhao, Kaiqun Li, Bin Yu\",\"doi\":\"10.1186/s10020-025-01202-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":18813,\"journal\":{\"name\":\"Molecular Medicine\",\"volume\":\"31 1\",\"pages\":\"177\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057237/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s10020-025-01202-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10020-025-01202-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
金黄色葡萄球菌(S. aureus)骨髓炎导致的骨质流失给骨科治疗带来了严重挑战,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。本研究采用γ-辐照杀伤金黄色葡萄球菌(γ-irradiation-killed S. aureus,简称IKSA)模拟炎症反应,探讨其引起全身骨质流失的机制。在本研究中,我们发现IKSA的系统应用通过增加破骨细胞和减少成骨细胞导致小鼠骨丢失。基于IKSA小鼠骨髓细胞的转录数据,确定了COX-2上调的免疫应答谱。在iksa处理的小鼠中,COX-2在骨髓免疫细胞(如髓源性抑制细胞(MDSCs)、中性粒细胞和巨噬细胞)中的表达广泛上调。机制上,COX-2刺激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,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减少。令人兴奋的是,小鼠和金黄色葡萄球菌骨髓炎患者骨髓中COX-2的表达也增加。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。
COX-2 inhibition as a therapeutic strategy for bone loss in Staphylococcus aureus osteomyelitis.
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.
期刊介绍:
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.