Dataset Information

Integrated Proteomics and Metabolomics Analysis of Sclerosis-Related Proteins and Femoral Head Necrosis Following Internal Fixation of Femoral Neck Fractures-1

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 analysis. We quantitatively identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Through Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined their roles. Our findings highlighted 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 common between the FHN and sclerosis groups, whereas the extracellular region and lysosome were prevalent between the FHN and FNF groups. The study also emphasized the PI3K-Akt pathway’s involvement in sclerosis and FHN, alongside key metabolic pathways implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Western blotting 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 analysis 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.

ORGANISM(S): Homo Sapiens

SUBMITTER: Pengcui Li

PROVIDER: PXD051808 | iProX | Sat Apr 27 00:00:00 BST 2024

REPOSITORIES: iProX

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Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures.

Liu Yang Y Ma Yongsheng Y Yang Wenming W Lin Qitai Q Xing Yugang Y Shao Huifeng H Li Pengcui P He Yong Y Duan Wangping W Wei Xiaochun X

Scientific reports 20240608 1

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 ...[more]

PMID: 38851808

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Project description:Enhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF-Î² signaling, and inflammatory pathway. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, Notch Signaling Pathway, natural killer cell mediated cytotoxicity, and B cell receptor signaling pathway, among others. The decreased group exclusively consists of genes involved in heme biosynthesis, p53 signaling pathway, and hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified. These data present the first temporal gene expression profiling analysis of the rat genome during intramembranous bone regeneration induced by femoral marrow ablation. In an Institutional Animal Care and Use Committee (IACUC) approved study, 27 adult male rats (Sprague Dawley, 400-425 g) were divided into nine groups: intact control (0 day), and 1, 3, 5, 7, 10, 14, 28, and 56 days post marrow ablation. Twenty-four animals received unilateral femoral ablation. At each time point, animals were killed in a carbon dioxide chamber, and whole femurs were harvested and denuded of soft tissue. For three samples per time point, both the distal and proximal ends of the femurs were cut off in order to exclude the epiphyses and growth plate regions. Diaphyseal marrow tissue and cells from the mid-shaft were flushed out using TrizolÂ®. Extracted RNA was homoginized and was prepared for hybridization. For each of the three samples per time point, gene expression was analyzed with GeneChipÂ® Rat Genome 230 2.0 Arrays (Affymetrix, Santa Clara, CA).

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Dataset Information

Integrated Proteomics and Metabolomics Analysis of Sclerosis-Related Proteins and Femoral Head Necrosis Following Internal Fixation of Femoral Neck Fractures-1

Publications

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures.

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