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Abstract：
Femoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.
摘要：
股骨头坏死（FHN）是股骨颈骨折（FNF）后的严重并发症，通常与螺旋路径周围的硬化有关。我们的研究旨在使用整合的蛋白质组学和代谢组学分析揭示FHN和硬化症的蛋白质组学和代谢组学基础。我们确定了三组之间的差异表达蛋白（DEP）和代谢物（DEM）：FNF患者（A组），硬化症（B组），和FHN（C组）。使用京都基因和基因组百科全书和基因本体论富集分析，我们研究了这些蛋白质和代谢物的作用。我们的发现强调了不同群体之间的显著差异，在硬化组和FNF组之间确定了218个DEP和44个DEM，FHN和硬化症组之间的247DEP和31DEM，FHN和FNF组之间有682个DEP和94个DEM。与碳酸盐脱水酶和水解酶相关的活性在FHN和硬化组中相似，而FHN和FNF组普遍存在胞外区域和溶酶体。我们的研究还强调PI3K-Akt途径参与硬化和FHN。此外，关键的代谢途径与甘油磷脂代谢和内源性大麻素的逆行信号有关.使用西方印迹,我们证实了特定基因/蛋白质如ITGB5，TNXB，CAII,硬化中的CAIII和FHN中的酸性磷酸酶5和组织蛋白酶K。这种全面的分析阐明了硬化和FHN背后的分子机制，并提出了潜在的生物标志物和治疗靶点。为改进治疗策略铺平道路。有必要进一步验证研究结果，以加强结果的稳健性和可靠性。
