褪黑素,一种治疗感染性骨不连的潜在有效药物。

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2023-09-27 DOI:10.1111/jpi.12914
Han-jun Qin, Si-ying He, Ke Shen, Qing-rong Lin, Yan-jun Hu, Zi-lin Chen, Bin Yu, Nan Jiang
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引用次数: 0

摘要

骨髓炎(OM)具有治疗的异质性和复杂性,感染复发的风险很高,可能导致肢体残疾。没有典型炎症症状的慢性非活动性骨髓炎(CIOM)的治疗对骨科医生来说是一个巨大的挑战。在对1091例OM病例进行数据分析的基础上,我们报告了CIOM患者潜在的成骨能力下降是二次手术的主要原因。我们的研究表明,CIOM患者成骨细胞能力受损与金黄色葡萄球菌内化引起的成骨细胞脱铁性贫血有关。进一步的研究表明,褪黑素可以通过Nox4/ROS/P38轴减轻感染状态下成骨细胞的脱铁性贫血,并保护CIOM患者的成骨能力。体内敲除NADPH氧化酶4(Nox4)可有效缓解感染状态下成骨细胞的脱铁性,促进成骨。通过大量临床数据分析结合分子实验,本研究阐明CIOM患者的隐性成骨性疾病与成骨细胞脱铁性贫血有关。我们发现褪黑素可能是CIOM患者的一种潜在治疗药物,并为OM的治疗提供了新的见解。
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Melatonin, a potentially effective drug for the treatment of infected bone nonunion

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.

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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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