Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head
Abstract Background Ferroptosis is implicated in various musculoskeletal conditions, including non-traumatic osteonecrosis of the femoral head (NT-ONFH). Objective The objective of this study was to explore the levels of two crucial proteins associated with ferroptosis, namely Glutathione peroxidase...
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BMC
2025-05-01
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| Series: | Journal of Orthopaedic Surgery and Research |
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| Online Access: | https://doi.org/10.1186/s13018-025-05912-y |
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| author | Qing-He Ye Peng Zhang Yong-Heng Zhao Wen-Xiu Zhu Hong-Xun Zhu Biao-Fang Wei |
| author_facet | Qing-He Ye Peng Zhang Yong-Heng Zhao Wen-Xiu Zhu Hong-Xun Zhu Biao-Fang Wei |
| author_sort | Qing-He Ye |
| collection | DOAJ |
| description | Abstract Background Ferroptosis is implicated in various musculoskeletal conditions, including non-traumatic osteonecrosis of the femoral head (NT-ONFH). Objective The objective of this study was to explore the levels of two crucial proteins associated with ferroptosis, namely Glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11), in both serum and femoral head samples, and to correlate their expression levels with the clinical severity of NT-ONFH. Methods The study included 136 NT-ONFH patients and an equal number of healthy controls. In addition, 68 subjects suffering from femoral neck fractures (FNF) were included in the study. The serum concentrations of GPX4 and SLC7A11 were quantified using the enzyme-linked immunosorbent assay. The GPX4 and SLC7A11 levels among tissue samples were identified through immunohistochemical staining, western blot analysis, and quantitative real-time polymerase chain reaction (qRT-PCR). The radiographic severity of the condition was evaluated utilizing the Association Research Circulation Osseous (ARCO) classification system, while the symptomatic severity was assessed utilizing the Visual Analogue Scale (VAS) alongside the Harris Hip Score (HHS). Results Patients diagnosed with NT-ONFH had considerably reduced serum concentrations of GPX4 and SLC7A11 in comparison to individuals in the healthy control group. Negative correlations of serum GPX4 and SLC7A11 levels with the ARCO stages were observed. A total of 73 ONFH and 68 FNF patients underwent total hip replacement. The mRNA and protein levels of GPX4 and SLC7A11 were lower in the necrotic areas compared to the non-necrotic areas and FNF femoral head tissues. Subsequent Receiver operating characteristic (ROC) curve analysis suggested that the decreased levels of both serum and local GPX4 and SLC7A11 could serve as potential biomarkers for the progression of ONFH. Furthermore, serum and local GPX4 and SLC7A11 levels were found to be negatively linked to the VAS score but positively related to the HHS score. Conclusion The levels of GPX4 and SLC7A11, both in serum and at the local site, were inversely correlated with the progression of NT-ONFH. Targeting ferroptosis and its associated proteins through potential therapeutic interventions could be a viable strategy to mitigate the severity of NT-ONFH. |
| format | Article |
| id | doaj-art-a096cc4fd9794a94b6f98408bfd6fe95 |
| institution | Kabale University |
| issn | 1749-799X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj-art-a096cc4fd9794a94b6f98408bfd6fe952025-08-20T03:53:57ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-05-0120111210.1186/s13018-025-05912-yDecreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral headQing-He Ye0Peng Zhang1Yong-Heng Zhao2Wen-Xiu Zhu3Hong-Xun Zhu4Biao-Fang Wei5Guangzhou University of Traditional Chinese MedicineGuangzhou University of Traditional Chinese MedicineGuangzhou University of Traditional Chinese MedicineGuangzhou University of Traditional Chinese MedicineGuangzhou University of Traditional Chinese MedicineLinyi People’s Hospital postgraduate training base of Guangzhou University of Traditional Chinese MedicineAbstract Background Ferroptosis is implicated in various musculoskeletal conditions, including non-traumatic osteonecrosis of the femoral head (NT-ONFH). Objective The objective of this study was to explore the levels of two crucial proteins associated with ferroptosis, namely Glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11), in both serum and femoral head samples, and to correlate their expression levels with the clinical severity of NT-ONFH. Methods The study included 136 NT-ONFH patients and an equal number of healthy controls. In addition, 68 subjects suffering from femoral neck fractures (FNF) were included in the study. The serum concentrations of GPX4 and SLC7A11 were quantified using the enzyme-linked immunosorbent assay. The GPX4 and SLC7A11 levels among tissue samples were identified through immunohistochemical staining, western blot analysis, and quantitative real-time polymerase chain reaction (qRT-PCR). The radiographic severity of the condition was evaluated utilizing the Association Research Circulation Osseous (ARCO) classification system, while the symptomatic severity was assessed utilizing the Visual Analogue Scale (VAS) alongside the Harris Hip Score (HHS). Results Patients diagnosed with NT-ONFH had considerably reduced serum concentrations of GPX4 and SLC7A11 in comparison to individuals in the healthy control group. Negative correlations of serum GPX4 and SLC7A11 levels with the ARCO stages were observed. A total of 73 ONFH and 68 FNF patients underwent total hip replacement. The mRNA and protein levels of GPX4 and SLC7A11 were lower in the necrotic areas compared to the non-necrotic areas and FNF femoral head tissues. Subsequent Receiver operating characteristic (ROC) curve analysis suggested that the decreased levels of both serum and local GPX4 and SLC7A11 could serve as potential biomarkers for the progression of ONFH. Furthermore, serum and local GPX4 and SLC7A11 levels were found to be negatively linked to the VAS score but positively related to the HHS score. Conclusion The levels of GPX4 and SLC7A11, both in serum and at the local site, were inversely correlated with the progression of NT-ONFH. Targeting ferroptosis and its associated proteins through potential therapeutic interventions could be a viable strategy to mitigate the severity of NT-ONFH.https://doi.org/10.1186/s13018-025-05912-yNon-traumatic osteonecrosis of femoral headGlutathione peroxidase 4Solute carrier family 7 member 11Disease severity |
| spellingShingle | Qing-He Ye Peng Zhang Yong-Heng Zhao Wen-Xiu Zhu Hong-Xun Zhu Biao-Fang Wei Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head Journal of Orthopaedic Surgery and Research Non-traumatic osteonecrosis of femoral head Glutathione peroxidase 4 Solute carrier family 7 member 11 Disease severity |
| title | Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head |
| title_full | Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head |
| title_fullStr | Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head |
| title_full_unstemmed | Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head |
| title_short | Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head |
| title_sort | decreased serum and local gpx4 and slc7a11 expression correlates with disease severity in non traumatic osteonecrosis of the femoral head |
| topic | Non-traumatic osteonecrosis of femoral head Glutathione peroxidase 4 Solute carrier family 7 member 11 Disease severity |
| url | https://doi.org/10.1186/s13018-025-05912-y |
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