Identification and assessment of novel dynamic biomarkers for monitoring non-traumatic osteonecrosis of the femoral head staging.
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SUBMITTER: Jia Y
PROVIDER: S-EPMC10265435 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
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Identification and assessment of novel dynamic biomarkers for monitoring non-traumatic osteonecrosis of the femoral head staging.
Jia Yan Y Zhang Yanqiong Y Li Shuwen S Li Ruihan R Li Weijie W Li Taixian T Wang Rongtian R Huang Guangrui G He Haijun H Lin Na N Chen Weiheng W
Clinical and translational medicine 20230601 6
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Project description:BackgroundGlucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease in osteoarticular surgery, with a high disability rate, which brings great physical and mental pain and economic burden to patients. Its specific pathogenesis has not been fully demonstrated, and there is a lack of recognized effective biomarkers for earlier detection and prompt treatment. This has become an urgent clinical problem for orthopedic scholars.Materials and methodsWe downloaded the gene expression profile dataset GSE123568 from the Gene Expression Omnibus database, used STRING and Cytoscape to carry out module analysis and built a gene interaction network. The four core genes most related to GIONFH in this network were ultimately found out by precise analysis and animal experiment were then conducted for verification. In this verification process, thirty-six New Zealand white rabbits were randomly divided into blank control group, model group and drug group. Except for the blank control group, the animal model of GIONFH was established by lipopolysaccharide and methylprednisolone, while the drug group was given the lipid-lowering drugs for intervention as planned. The rabbits were taken for magnetic resonance imaging at different stages, and their femoral head specimens were taken for pathological examination, then the expression of target genes in the femoral head specimens of corresponding groups was detected. Validation methods included RT-PCR and pathological examination.ResultsA total of 679 differential genes were selected at first, including 276 up-regulated genes and 403 down-regulated genes. Finally, four genes with the highest degree of correlation were screened. Animal experiment results showed that ASXL1 and BNIP3L were in low expression, while FCGR2A and TYROBP were highly expressed.ConclusionThrough animal experiments, it was confirmed that ASXL1, BNIP3L, FCGR2A and TYROBP screened from the comparative analysis of multiple genes in the database were closely related to GIONFH, which is important for early diagnosis of Glucocorticoid-induced osteonecrosis of the femoral head.
| S-EPMC9832261 | biostudies-literature
Project description:Non-traumatic osteonecrosis of the femoral head (NONFH) remains a common refractory disease with poorly understood pathogenesis. Macrophage M1/M2 imbalance and chronic inflammatory microenvironment have been suggested to be closely related to osteonecrosis. Here we describe direct visual evidence for the involvement of dynamic changes in macrophages and the chronic inflammatory microenvironment in human NONFH. Osteonecrosis induces inflammatory responses and macrophage enrichment in the reparative area, and the number of inflammatory cells and macrophages falls during progressive-to end-stage NONFH. Multiplex immunohistochemistry demonstrated that macrophage M1/M2 ratio increased from 3 to 10 during progressive-to end-stage. During the progressive-stage, new blood vessels formed in the reparative area, M2 macrophages accumulated in perivascular (M1/M2 ratio ∼0.05), while M1 macrophages were enriched in avascular areas (M1/M2 ratio ∼12). Furthermore, inflammatory cytokines were detected in synovial fluid and plasma using cytometric bead arrays. Interleukin (IL)-6 and IL-1β were persistently enriched in synovial fluid compared to plasma in patients with NONFH, and this difference was confirmed by immunohistochemistry staining. However, only IL-6 levels in plasma were higher in patients with progressive-stage NONFH than in osteoarthritis. Moreover, fibrosis tissues were observed in the necrotic area in progressive-stage and end-stage NONFH based on Sirius Red staining. Together, these findings indicate that macrophage M1/M2 imbalance facilitates the progression of NONFH, a chronic inflammatory disease characterized by chronic inflammation, osteonecrosis and tissue fibrosis in the local lesion. Inhibiting inflammation, promoting the resolution of inflammation, switching macrophages to an M2 phenotype, or inhibiting their adoption of an M1 phenotype may be useful therapeutic strategies against NONFH.
| S-EPMC9094367 | biostudies-literature
Project description:Early diagnosis and prompt treatment are the key to prevent collapse and delay Steroid-induced Osteonecrosis of the Femoral Head(SONFH) progression.The aim of this study was to identify potential biomarkers for the diagnosis of SONFH, so to improve the efficiency of early diagnosis. Microarray analysis based on the 30 SONFH patients and 10 non-SONFH patients(following steroid administration) was performed to screen SONFH-related genes.
2019-12-31 | GSE123568 | GEO
Project description:BackgroundThis study was aimed to identify key ferroptosis-related biomarkers in steroid-induced osteonecrosis of the femoral head (SONFH) based on machine learning algorithm.MethodsThe SONFH dataset GSE123568 (including 30 SONFH patients and 10 controls) was used in this study. The differentially expressed genes (DEGs) were selected between SONFH and control groups, which were subjected to WGCNA. Ferroptosis-related genes were downloaded from FerrDb V2, which were then compared with DEGs and module genes. Two machine learning algorithms were utilized to identify key ferroptosis-related genes, and the underlying mechanisms were analyzed by GSEA. Correlation analysis between key ferroptosis-related genes and immune cells was analyzed by Spearman method. The drug-gene relationships were predicted in CTD.ResultsTotal 2030 DEGs were obtained. WGCNA identified two key modules and obtained 1561 module genes. Finally, 43 intersection genes were identified as disease-related ferroptosis-related genes. After LASSO regression and RFE-SVM algorithms, 4 intersection genes (AKT1S1, BACH1, MGST1 and SETD1B) were considered as key ferroptosis-related gene. The 4 genes were correlated with osteoclast differentiation pathway. Twenty immune cells with significant differences were obtained between the groups, and the 4 key ferroptosis-related genes were correlated with most immune cells. In CTD, 41 drug-gene relationship pairs were finally obtained.ConclusionsThe 4 key ferroptosis-related genes, AKT1S1, BACH1, MGST1 and SETD1B, were identified to play a critical role in SONFH progression through osteoclast differentiation and immunologic mechanisms. Additionally, all the 4 genes had good disease prediction effect and could act as biomarkers for the diagnosis and treatment of SONFH.
| S-EPMC10148479 | biostudies-literature
Project description:ObjectivesUrinary microRNAs (miRNAs) have shown great diagnostic and prognostic values for multiple diseases. The profile of urinary miRNAs in patients with idiopathic osteonecrosis of femoral head (ONFH) is currently unclear.MethodsWe first randomly chose ten patients with each Association Research Circulation Osseous (ARCO) stage (I, II, III and IV) and ten healthy participants from the entire cohorts for initial screening. The miRNA polymerase chain reaction (PCR) array was then performed to identify the differentially abundant miRNAs in urine of these participants. We then verified the findings in the entire cohort. Clinical features including age, gender, bone mass index (BMI), lesion size and stages were recorded. We then analysed the association between the level of urinary miRNAs and clinical features.ResultsOur data indicated that there were 13 differentially abundant miRNAs among all groups. Urinary miR-150 demonstrated the highest diagnostic value among all candidates. Urinary miR-185 and miR-133a increased by ARCO staging. The levels of urinary miR-4824 abruptly decreased after femoral head collapse (ARCO stage III and IV). Urinary miR-144 was the only marker that correlated with lesion size.ConclusionsThe levels of urinary miRNAs are valuable biomarkers for idiopathic ONFH. Given the noninvasive nature of this test, it is potentially useful for diagnosis and monitoring of idiopathic ONFH progression.The translational potential of this articleThis article gives novel methods for ONFH diagnosis and progression monitoring in a convenient and non-invasive way.
| S-EPMC7773953 | biostudies-literature
Project description:PurposeSteroid-induced necrosis of the femoral head (SONFH) is a refractory orthopedic hip disease occurring in young and middle-aged people, with glucocorticoids being the most common cause. Previous experimental studies have shown that cell pyroptosis may be involved in the pathological process of SONFH, but its pathogenesis in SONFH is still unclear. This study aims to screen and validate potential pyroptosis-related genes in SONFH diagnosis by bioinformatics analysis to further elucidate the mechanism of pyroptosis in SONFH.MethodsThere were 33 pyroptosis-related genes obtained from the prior reviews. The mRNA expression was downloaded from GSE123568 dataset in the Gene Expression Omnibus (GEO) database, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples. The pyroptosis-related differentially expressed genes involved in SONFH were identified with "affy" and "limma" R package by intersecting the GSE123568 dataset with pyroptosis genes. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the pyroptosis-related differentially expressed genes involved in SONFH were conducted by "clusterProfiler" R package and visualized by "GOplot" R package. Then, the correlations between the expression levels of the pyroptosis-related differentially expressed genes involved in SONFH were confirmed with "corrplot" R package. Moreover, the protein-protein interaction (PPI) network was analysed by using GeneMANIA database. Next, The ROC curve of pyroptosis-related differentially expressed genes were analyzed by "pROC" R package.ResultsA total of 10 pyroptosis-related differentially expressed genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 20 upregulated genes and 10 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 10 pyroptosis-related differentially expressed genes involved in SONFH were particularly enriched in cysteine-type endopeptidase activity involved in apoptotic process, positive regulation of interleukin-1 beta secretion and NOD-like receptor signaling pathway. Correlation analysis revealed significant correlations among the 10 differentially expressed pyroptosis-related genes involved in SONFH. The PPI results demonstrated that the 10 pyroptosis-related differentially expressed genes interacted with each other. Compared to non-SONFH samples, these pyroptosis-related differentially expressed genes had good predictive diagnostic efficacy (AUC = 1.000, CI = 1.000-1.000) in the SONFH samples, and NLRP1 had the highest diagnostic value (AUC: 0.953) in the SONFH samples.ConclusionsThere were 10 potential pyroptosis-related differentially expressed genes involved in SONFH were identified via bioinformatics analysis, which might serve as potential diagnostic biomarkers because they regulated pyroptosis. These results expand the understanding of SONFH associated with pyroptosis and provide new insights to further explore the mechanism of action and diagnosis of pyroptosis associated in SONFH.
| S-EPMC10367407 | biostudies-literature
Project description:We observed 21 prominent protein spots that differed between the two groups. Three of these proteins were upregulated and the rest 18 proteins were downregulated in patients with steroid-induced ONFH. The spots determined in the steroid-induced ONFH and health control groups were replicable.The spot no. 21 corresponding to an upregulated protein in patients with steroid-induced ONFH was identified as SAA.
2022-02-15 | PXD028318 | Pride
Project description:BackgroundThe 2019 Revised Association Research Circulation Osseous (ARCO) Staging Criteria for Osteonecrosis of the Femoral Head (ONFH) only requires plain radiographs and magnetic resonance imaging (MRI) to diagnose and stage ONFH; however, the effectiveness of the 2019 ARCO criteria in the absence of computed tomography (CT) scans has not been investigated. Therefore, the purpose of this study was to evaluate whether CT scanning is a necessary modality for diagnosing/staging ONFH using the ARCO staging system. More specifically, do CT scans help differentiate pre- and post-collapse lesions more than MRI scans?MethodsA study was conducted on 228 ONFH patients diagnosed between January 1, 2008, and December 31, 2018, at a single academic medical center. CT and MRI scans were reviewed by the senior author and other contributors. The ONFH classification was compared between the 2 scans to determine if CT scans were able to further differentiate staging of collapsed lesions vs MRI scans.ResultsA diagnosis of ONFH was made by MRI first in 57% (129/228) while 21% (48/228) used MRI and CT simultaneously. Only 22% (51/228) of cases were diagnosed by CT scans first. There were no cases where collapse was found by a CT scan that were not diagnosed by standard x-rays and/or MRIs.ConclusionsCT scans are not a useful adjunct for diagnosing or treating ONFH and are not necessary if MRI is ordered when using the Revised ARCO Staging System for ONFH diagnosis.
| S-EPMC10585620 | biostudies-literature
Project description:ObjectiveThis study aimed to identify key diagnostic markers and immune infiltration of (SONFH) by bioinformatics analysis.MethodsRelated SONFH datasets were downloaded from the Gene Expression Omnibus (GEO) database. First, we identified the differentially expressed genes (DEGs) and performed the functional enrichment analysis. Then weighted correlation network analysis (WGCNA) and the MCODE plug-in in Cytoscape were used to identify the diagnostic markers of SONFH. Finally, CIBERSORT was used to analyze the immune infiltration between SONFH and healthy controls, and the correlation between infiltrating immune cells and diagnostic markers was analyzed.ResultsTYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be key diagnostic markers of SONFH. Immune cell infiltration analysis revealed that Memory B cells and activated dendritic cells may be related to the SONFH process. Moreover, HCK was negatively correlated with CD8 T cells, and neutrophils were positively correlated with those key diagnostic markers.ConclusionsTYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be used as diagnostic markers of SONFH, and immune-related mechanism of SONFH and the potential immunotherapy are worthy of further study.
| S-EPMC8767711 | biostudies-literature
Project description:Osteonecrosis of the femoral head (ONFH) is a condition caused by a disruption or damage to the femoral head's blood supply, which causes the death of bone cells and bone marrow components and prevents future regeneration. Ferroptosis, a type of controlled cell death, is caused by iron-dependent lipid peroxidation. Here, we identified ferroptosis-related genes and infiltrating immune cells involved in ONFH and predicted the underlying molecular mechanisms. The GSE123568 dataset was subjected to differential expression analysis to identify genes related to ferroptosis. Subsequently, GO and KEGG pathway enrichment analyses, as well as protein-protein interaction (PPI) network analysis, were conducted. Hub genes involved in ferroptosis were identified using machine learning and other techniques. Additionally, immune infiltration analysis and lncRNA-miRNA-mRNA network prediction analysis were performed. Finally, we determined whether ferroptosis occurred by measuring iron content. The hub genes were validated by ROC curve analysis and qRT-PCR. Four ferroptosis-related hub genes (MAPK3, PTGS2, STK11, and SLC2A1) were identified. Additionally, immune infiltration analysis revealed a strong correlation among ONFH, hub genes, and various immune cells. Finally, we predicted the network relationship between differentially expressed lncRNAs and hub genes in the lncRNA-miRNA-mRNA network. MAPK3, PTGS2, STK11, and SLC2A1 have been identified as potential ferroptosis-related biomarkers and drug targets for the diagnosis and prognosis of ONFH, while some immune cells, as well as the interaction between lncRNA, miRNA, and mRNA, have also been identified as potential pathogenesis markers and therapeutic targets.
| S-EPMC10909969 | biostudies-literature