Mass Spectrometry Characterization of the Human Ankle and Hindfoot Fracture Microenvironment in Young and Aged Subjects.

IF 1.1 4区 医学 Q3 ORTHOPEDICS Indian Journal of Orthopaedics Pub Date : 2024-11-05 eCollection Date: 2024-12-01 DOI:10.1007/s43465-024-01284-3
John F Dankert, Devan D Mehta, Tori C Rodrick, Evgeny Kanshin, Rown Parola, Beatrix M Ueberheide, Drew R Jones, Kenneth A Egol, Philipp Leucht
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Abstract

Background: Bone regeneration following a fracture is dependent on multiple factors including skeletal stem cells (SSCs). Recruitment, proliferation, and differentiation of the SSCs is guided by the proteins and metabolites found within the fracture microenvironment. Understanding how intrinsic factors affect the fracture microenvironment has been a topic of ongoing investigation. This study sought to determine whether the levels of select proteins and metabolites within the fracture hematoma would be differentially expressed depending on the age of the patient. We hypothesized that a distinct set of proteins and metabolites found within the fracture hematoma microenvironment would be present at varying levels depending on patient age.

Methods: The research study was reviewed and approved by an Institutional Review Board. Hematomas were collected from subjects aged 18 years old or older undergoing surgical intervention for a fracture. Hematoma samples were selected from the biorepository and assigned to one of two fracture groups including young ankle/hindfoot and aged ankle/hindfoot. Protein and metabolite levels within each hematoma were analyzed by liquid chromatography-mass spectrometry.

Results: A total of seven hematomas were included in each the young ankle/hindfoot and aged ankle/hindfoot groups. From the global metabolomic analysis, creatine, 2-methylindoline, and acetyl-L-carnitine were identified as being differentially expressed between both groups. An untargeted metabolomic analysis of the two groups identified significant differences in the levels of an additional 66 metabolites. Proteomic analysis identified 34 proteins that were expressed at significantly different levels.

Conclusions: The level of metabolites and proteins found within the local fracture environment vary by patient age. Future investigations will focus on identifying a role for these proteins and metabolites in bone homeostasis and fracture healing.

Level of evidence: N/A, basic science investigation.

Supplementary information: The online version contains supplementary material available at 10.1007/s43465-024-01284-3.

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年轻人和老年人踝关节和后足骨折微环境的质谱分析。
背景:骨折后的骨再生依赖于多种因素,包括骨干细胞(ssc)。断裂微环境中的蛋白质和代谢物引导着ssc的募集、增殖和分化。了解内在因素如何影响裂缝微环境一直是研究的主题。本研究旨在确定骨折血肿中选择的蛋白质和代谢物的水平是否会根据患者的年龄而差异表达。我们假设在骨折血肿微环境中发现的一组不同的蛋白质和代谢物会根据患者的年龄以不同的水平存在。方法:该研究由机构审查委员会审查并批准。血肿收集自18岁或以上接受骨折手术干预的受试者。从生物库中选择血肿样本,并将其分为两个骨折组,包括年轻踝关节/后足和老年踝关节/后足。用液相色谱-质谱法分析每个血肿内的蛋白质和代谢物水平。结果:幼踝关节/后足组和老年踝关节/后足组各有7个血肿。从整体代谢组学分析,肌酸,2-甲基林多林和乙酰左旋肉碱被确定为两组之间的差异表达。对两组进行的非靶向代谢组学分析发现,另外66种代谢物的水平存在显著差异。蛋白质组学分析鉴定出34个表达水平显著不同的蛋白。结论:局部骨折环境中发现的代谢物和蛋白质水平因患者年龄而异。未来的研究将集中在确定这些蛋白质和代谢物在骨稳态和骨折愈合中的作用。证据等级:无,基础科学调查。补充资料:在线版本包含补充资料,下载地址:10.1007/s43465-024-01284-3。
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来源期刊
CiteScore
1.80
自引率
0.00%
发文量
185
审稿时长
9 months
期刊介绍: IJO welcomes articles that contribute to Orthopaedic knowledge from India and overseas. We publish articles dealing with clinical orthopaedics and basic research in orthopaedic surgery. Articles are accepted only for exclusive publication in the Indian Journal of Orthopaedics. Previously published articles, articles which are in peer-reviewed electronic publications in other journals, are not accepted by the Journal. Published articles and illustrations become the property of the Journal. The copyright remains with the journal. Studies must be carried out in accordance with World Medical Association Declaration of Helsinki.
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