年轻和老年受试者人踝关节和后足骨折微环境的质谱表征
Mass Spectrometry Characterization of the Human Ankle and Hindfoot Fracture Microenvironment in Young and Aged Subjects.
作者信息
Dankert John F, Mehta Devan D, Rodrick Tori C, Kanshin Evgeny, Parola Rown, Ueberheide Beatrix M, Jones Drew R, Egol Kenneth A, Leucht Philipp
机构信息
Department of Orthopedic Surgery, NYU Grossman School of Medicine, NYU Langone Orthopedic Hospital, 550 First Avenue, MSB 251, New York, NY 10016 USA.
Metabolomics Core Resources Laboratory, NYU Langone Health, New York, NY USA.
出版信息
Indian J Orthop. 2024 Nov 5;58(12):1871-1882. doi: 10.1007/s43465-024-01284-3. eCollection 2024 Dec.
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.
背景
骨折后的骨再生取决于多种因素，包括骨骼干细胞（SSCs）。SSCs的募集、增殖和分化受骨折微环境中发现的蛋白质和代谢产物的引导。了解内在因素如何影响骨折微环境一直是正在进行的研究课题。本研究旨在确定骨折血肿中特定蛋白质和代谢产物的水平是否会因患者年龄而差异表达。我们假设，根据患者年龄，骨折血肿微环境中发现的一组独特的蛋白质和代谢产物会以不同水平存在。
方法
该研究经机构审查委员会审查并批准。从18岁及以上因骨折接受手术干预的受试者中收集血肿。从生物样本库中选择血肿样本，并分配到两个骨折组之一，包括年轻踝关节/后足组和老年踝关节/后足组。通过液相色谱-质谱法分析每个血肿中的蛋白质和代谢产物水平。
结果
年轻踝关节/后足组和老年踝关节/后足组各纳入7个血肿。通过整体代谢组学分析，发现肌酸、2-甲基吲哚啉和乙酰-L-肉碱在两组之间差异表达。对两组进行的非靶向代谢组学分析确定了另外66种代谢产物水平存在显著差异。蛋白质组学分析确定了34种表达水平有显著差异的蛋白质。
结论
局部骨折环境中发现的代谢产物和蛋白质水平因患者年龄而异。未来的研究将集中于确定这些蛋白质和代谢产物在骨稳态和骨折愈合中的作用。
证据水平
无，基础科学研究。
补充信息
在线版本包含可在10.1007/s43465-024-01284-3获取的补充材料。
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