Groven Rald V M, Kuik Christel, Greven Johannes, Mert Ümit, Bouwman Freek G, Poeze Martijn, Blokhuis Taco J, Huber-Lang Markus, Hildebrand Frank, Cillero-Pastor Berta, van Griensven Martijn
Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.
Division of Trauma Surgery, Department of Surgery, Maastricht University Medical Center+, Maastricht, Netherlands.
Bone Joint Res. 2024 May 3;13(5):214-225. doi: 10.1302/2046-3758.135.BJR-2023-0323.R1.
The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.
A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase.
The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes.
The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma.
本研究旨在通过无标记蛋白质组学确定多发伤后的骨折血肿蛋白质组，比较两种不同的骨折治疗策略。
采用猪多发伤模型，比较两种骨折治疗策略：早期全面治疗（ETC）和损伤控制骨科（DCO）。采集骨折血肿并使用液相色谱-串联质谱进行分析。每组鉴定出有鉴别意义的蛋白质，并进行蛋白质相互作用分析，以进一步阐明骨折早期愈合阶段的关键生物分子途径。
早期骨折血肿蛋白质组的特征是免疫调节蛋白、成骨蛋白以及参与凝血级联反应的蛋白。观察到了治疗特异性的蛋白质组改变。ETC组的骨折血肿蛋白质组显示与补体系统激活、中性粒细胞功能和巨噬细胞激活等相关的促炎蛋白表达增加，而成骨和组织重塑相关蛋白表达降低。相反，DCO组的骨折血肿蛋白质组包含各种上调或仅检测到的与组织再生和重塑相关的蛋白，以及与抗炎和成骨过程相关的蛋白。
ETC组早期骨折血肿蛋白质组的特征是免疫调节蛋白（主要是促炎蛋白）的表达，而DCO组早期骨折血肿蛋白质组本质上更具再生性和成骨性。这些发现与临床观察结果相符，即多发伤后手术创伤增加会导致炎症失衡，可能导致组织再生减少，并为严重创伤后骨折愈合的调节机制提供了见解。
