Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis
BackgroundOsteoarthritis (OA) is a widespread disorder affecting joints, recognized for cartilage wear and inflammatory responses, which substantially affects patients’ quality of life. This research aim to discover amino acid metabolism-related differentially expressed genes (AAMRDEGs) and clarify...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1588072/full |
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| author | Zhenghuan Zhu Jiaqing Meng Junfeng Hu Lingmin Hu Wenge Ding Wanchao Zhang Chuang Zhao Lin Feng Kejie Wang |
| author_facet | Zhenghuan Zhu Jiaqing Meng Junfeng Hu Lingmin Hu Wenge Ding Wanchao Zhang Chuang Zhao Lin Feng Kejie Wang |
| author_sort | Zhenghuan Zhu |
| collection | DOAJ |
| description | BackgroundOsteoarthritis (OA) is a widespread disorder affecting joints, recognized for cartilage wear and inflammatory responses, which substantially affects patients’ quality of life. This research aim to discover amino acid metabolism-related differentially expressed genes (AAMRDEGs) and clarify their functions in OA pathogenesis.MethodsHerein, we conducted an analysis of combined GEO datasets (GSE55457, GSE55235, and GSE12021), identifying 169 AAMRDEGs and indicating their importance in chondrocyte function and inflammation. Furthermore, significant correlations were observed between various immune cell types, underscoring the intricate function of the immune system in OA. Thereafter, we developed highly accurate diagnostic models using LASSO regression and SVM methodologies, achieving an area under the curve > 0.9. Protein-protein interaction analysis revealed significant interactions among MTHFD2, PPP1R15A, SLC2A4, and WNT5B, with their expression levels corroborated using single-cell datasets, highlighting the potential therapeutic targets. To confirm the presence of these hub AAMRGs, real-time polymerase chain reaction and immunohistochemistry were employed.ResultsWe identified 2,115 DEGs between OA and control groups, with 1,062 upregulated and 1,053 downregulated. Enrichment analysis linked AAMRDEGs to amino acid catabolism and multiple KEGG pathways, indicating their importance in chondrocyte function and inflammation. Furthermore, significant correlations were observed between various immune cell types, underscoring the intricate role of the immune system in OA. Subsequently, we developed highly accurate diagnostic models using LASSO regression and SVM methodologies, achieving an area under the curve > 0.9. Protein-protein interaction analysis revealed significant interactions among MTHFD2, PPP1R15A, SLC2A4, and WNT5B, with their expression levels corroborated using single-cell datasets, highlighting the potential therapeutic targets. Real-time polymerase chain reaction and immunohistochemistry were used to validate the expression of these hub amino acid metabolism-related genes.ConclusionThis investigation presents a detailed evaluation of AAMRGs in OA, highlighting their roles in disease pathogenesis and offering new insights for therapeutic research. Key genes SLC2A4, MTHDF2, and WNT5B might function as markers for early identification and personalized OA treatment. |
| format | Article |
| id | doaj-art-3e8a698c091845338652cb7b1f9e235f |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-3e8a698c091845338652cb7b1f9e235f2025-08-20T03:17:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15880721588072Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritisZhenghuan Zhu0Jiaqing Meng1Junfeng Hu2Lingmin Hu3Wenge Ding4Wanchao Zhang5Chuang Zhao6Lin Feng7Kejie Wang8Department of Orthopedics, Changzhou First People’s Hospital, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaDepartment of Orthopedics, Changzhou First People’s Hospital, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaDepartment of Orthopedics, Changzhou First People’s Hospital, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaDepartment of Reproduction, Changzhou Maternity and Child Health Care Hospital, Changzhou, Jiangsu, ChinaDepartment of Orthopedics, Changzhou First People’s Hospital, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaDepartment of Surgery, Wuqia County People’s Hospital, Uqia, Xinjiang, ChinaDepartment of Surgery, Wuqia County People’s Hospital, Uqia, Xinjiang, ChinaDepartment of Surgery, Wuqia County People’s Hospital, Uqia, Xinjiang, ChinaDepartment of Orthopedics, Changzhou First People’s Hospital, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaBackgroundOsteoarthritis (OA) is a widespread disorder affecting joints, recognized for cartilage wear and inflammatory responses, which substantially affects patients’ quality of life. This research aim to discover amino acid metabolism-related differentially expressed genes (AAMRDEGs) and clarify their functions in OA pathogenesis.MethodsHerein, we conducted an analysis of combined GEO datasets (GSE55457, GSE55235, and GSE12021), identifying 169 AAMRDEGs and indicating their importance in chondrocyte function and inflammation. Furthermore, significant correlations were observed between various immune cell types, underscoring the intricate function of the immune system in OA. Thereafter, we developed highly accurate diagnostic models using LASSO regression and SVM methodologies, achieving an area under the curve > 0.9. Protein-protein interaction analysis revealed significant interactions among MTHFD2, PPP1R15A, SLC2A4, and WNT5B, with their expression levels corroborated using single-cell datasets, highlighting the potential therapeutic targets. To confirm the presence of these hub AAMRGs, real-time polymerase chain reaction and immunohistochemistry were employed.ResultsWe identified 2,115 DEGs between OA and control groups, with 1,062 upregulated and 1,053 downregulated. Enrichment analysis linked AAMRDEGs to amino acid catabolism and multiple KEGG pathways, indicating their importance in chondrocyte function and inflammation. Furthermore, significant correlations were observed between various immune cell types, underscoring the intricate role of the immune system in OA. Subsequently, we developed highly accurate diagnostic models using LASSO regression and SVM methodologies, achieving an area under the curve > 0.9. Protein-protein interaction analysis revealed significant interactions among MTHFD2, PPP1R15A, SLC2A4, and WNT5B, with their expression levels corroborated using single-cell datasets, highlighting the potential therapeutic targets. Real-time polymerase chain reaction and immunohistochemistry were used to validate the expression of these hub amino acid metabolism-related genes.ConclusionThis investigation presents a detailed evaluation of AAMRGs in OA, highlighting their roles in disease pathogenesis and offering new insights for therapeutic research. Key genes SLC2A4, MTHDF2, and WNT5B might function as markers for early identification and personalized OA treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1588072/fullosteoarthritisamino acid metabolism genesweighted gene co-expression network analysisimmunity-related genesimmune infiltrationlasso regression |
| spellingShingle | Zhenghuan Zhu Jiaqing Meng Junfeng Hu Lingmin Hu Wenge Ding Wanchao Zhang Chuang Zhao Lin Feng Kejie Wang Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis Frontiers in Immunology osteoarthritis amino acid metabolism genes weighted gene co-expression network analysis immunity-related genes immune infiltration lasso regression |
| title | Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis |
| title_full | Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis |
| title_fullStr | Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis |
| title_full_unstemmed | Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis |
| title_short | Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis |
| title_sort | exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis |
| topic | osteoarthritis amino acid metabolism genes weighted gene co-expression network analysis immunity-related genes immune infiltration lasso regression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1588072/full |
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