Single-cell RNA sequencing reveals chondrocyte heterogeneity and fibrocartilage transition in osteonecrosis of the femoral head
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE311084 | GEO | 2026/06/17
REPOSITORIES: GEO
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Project description:Osteonecrosis of the femoral head (ONFH) remains a devastating complication of glucocorticoid therapy and alcohol abuse, yet the pathophysiology is poorly understood. Using single-cell RNA sequencing, we analyzed femoral head specimens from patients undergoing total hip arthroplasty due to steroid-induced ONFH, alcohol-induced ONFH, or hip osteoarthritis (OA). Our comprehensive analysis across conditions revealed etiology-specific cellular compositions and transcriptional profiles. Steroid-induced ONFH demonstrated a distinctive immunological signature characterized by a neutrophil-predominant, elevated innate-to-adaptive immune cell ratio compared to alcohol-induced ONFH or OA. T cell analysis revealed impaired maturation in steroid-induced ONFH, with abundant naïve T cells but reduced mature CD4+ T cells and CD4+ memory T cells compared to both alcohol-induced ONFH and OA. In addition, compared to alcohol-induced ONFH, steroid-induced ONFH was associated with an increase in exhausted/dysfunctional CD8+ T cells which suggests an impaired response to stress and reflects chronic immune dysfunction. Within stromal cell populations, steroid-induced ONFH demonstrated an increase in pericytes, endothelial cells, and mesenchymal cell with osteogenic features as compared to both alcohol-induced ONFH or OA. These findings collectively reveal novel cellular mechanisms underlying steroid-induced ONFH which may contribute to further investigation of etiology-specific pathogenesis and treatment strategies.
2026-01-21 | GSE316957 | GEO
Project description:Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (84.7%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.33; 95% confidence interval: 1.36-13.76) of having coagulation abnormalities than did those without the mutation (wild-type) (p = 0.008). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. SNP genotype analysis of Affymetrix 6.0 Chip. SNP arrays was performed for 22 Chinese patients with Osteonecrosis of the Femoral Head.
2014-07-28 | E-GEOD-58951 | biostudies-arrayexpress
Project description:Aims: Steroid-induced osteonecrosis of the femoral head (SIONFH) is a debilitating condition often accompanied by cystic change in the affected bone. Previous studies and our clinical observation have suggested the potential for tissue repair within the cystic change, but the underlying cellular mechanisms remain unclear. This study aims to investigate the heterogeneity of cells in the cystic change region, focusing on chondrocytes and endothelial cells, using single-cell RNA sequencing (scRNA-seq) and subsequent histological validation. Method: Cystic change tissues were obtained from patients undergoing total hip arthroplasty. Single-cell RNA sequencing was performed to identify distinct cell populations, particularly chondrocytes and endothelial cells. Alcian blue staining was employed to detect chondrocytes, while immunohistochemistry (IHC) was used to verify the presence of repair-associated chondrocytes. Additionally, HE staining was performed to further analyze tissue architecture like blood vessels. Results: ScRNA-seq analysis identified two major cell types in the cystic change region: endothelial cells involved in angiogenesis and chondrocytes, which included subpopulations associated with cartilage repair. Alcian blue staining showed strong cartilage matrix staining within the cystic change. Immunohistochemistry further validated the expression of repair-associated markers in the chondrocyte population, suggesting active cartilage repair. Cellular communication analysis revealed intercellular interactions between reparative chondrocyte via matrix proteins (FN1, COL1A1) and integrin receptors on angiogenic endothelial cell, suggesting their potential collaboration in the repair process. Conclusion: This study highlights the positive effects of cystic change region of SIONFH in the process of repair based on clinical observations and single-cell RNA sequencing technology. The presence of functionally distinct cell populations, including angiogenic endothelial cells and repair-associated chondrocytes, within cystic change region of SIONFH. The findings suggest a biological basis for repair in the cystic change tissue, providing insights that may inform future therapeutic strategies targeting bone and cartilage regeneration in osteonecrosis.
2025-09-24 | GSE290411 | GEO
Project description:Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (84.7%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.33; 95% confidence interval: 1.36-13.76) of having coagulation abnormalities than did those without the mutation (wild-type) (p = 0.008). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.
2014-07-28 | GSE58951 | GEO
Project description:The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomics profile of ONFH cartilage with that of normal controls
2021-01-20 | PXD023698 |
Project description:Subchondral bone samples from six patients who underwent primary total hip arthroplasty (three ONFH patients and three patients in control group with femoral neck fracture) were obtained.
2022-03-12 | E-MTAB-11493 | biostudies-arrayexpress
Project description:We recently showed that microRNA different profile from Trauma-induced osteonecrosis of the femoral head (TIONFH) and healing patients.
2017-09-14 | GSE89587 | GEO
Project description:<p><strong>AIMS:</strong> Although studies have made the connection between lipid metabolism disorder and osteonecrosis of the femoral head (ONFH), the characteristics of the circulating lipidome signature of ONFH have not yet been investigated yet and need to be explored.</p><p><strong>METHODS:</strong> We conducted a comprehensive analysis of plasma lipidomics in a clinical human cohort including 32 healthy normal control (NC) subjects and 91 ONFH patients in different subgroups (alcohol-induced [AONFH], steroid-induced, and traumatic ONFH) and stages (stages I/II, stages III/IV), using ultra-high performance liquid chromatography–tandem mass spectrometry.</p><p><strong>RESULTS:</strong> The PLS-DA model indicates that the global plasma lipidome profile differs between the ONFH and NC samples. We identified a signature including 22 common differentially expressed lipids (DELs) in all the three subgroups (VIP > 1, P < 0.05, FC > 1.5 or FC < 0.67, compared with the NC group), and for each of the subtype-specific lipidome profiles, as well as altered lipid biomarkers (FC > 2, P < 0.05, and AUC > 0.7, compared with the NC group) for each subgroup. The AONFH subgroup has the most DELs, and the plasma levels of lipid compounds in the subclass of triacylglycerol increased obviously in the AONFH samples. We identified that 9 stage-positive and 2 stage-negative lipids may function as novel biomarkers that predict the disease progression of ONFH.</p><p><strong>CONCLUSION:</strong> This study provides the first overview, analysis, and understanding of the unique phenotype-related plasma lipidome signature of ONFH. The results will offer insights into the mechanisms underlying lipid metabolism in the pathogenesis and progression of ONFH, and will help to identify novel lipids biomarkers or targets for disease diagnosis and treatment.</p>
2021-07-06 | MTBLS2262 | MetaboLights
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: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