Ning Xu, Gongwu Yuan, Wenbo Zeng, Ximing Liu, M A Wan, Suyang Xu, Yikang Bi, Hai Hu, Yafeng Xu, Shenghui Lan
{"title":"吉非替尼通过抑制EGFR通路和对抗sox9驱动的骨代谢重编程促进骨折愈合。","authors":"Ning Xu, Gongwu Yuan, Wenbo Zeng, Ximing Liu, M A Wan, Suyang Xu, Yikang Bi, Hai Hu, Yafeng Xu, Shenghui Lan","doi":"10.21873/invivo.13942","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>To investigate the role of epidermal growth factor receptor (EGFR) inhibition in enhancing bone fracture healing by modulating box transcription factor 9 (SOX9) and bone metabolism.</p><p><strong>Materials and methods: </strong>A rat femoral fracture model was used. Techniques included histological analysis, X-ray scoring, micro-computed tomography, immunohistochemistry, and biomechanical testing. Serum markers were analyzed with enzyme-linked immunosorbent assay, while quantitative real-time polymerase chain reaction and western blotting assessed molecular pathways. Metabolic changes were measured using a Seahorse analyzer. An EGFR inhibitor, gefitinib, was used to examine its impact on periosteal stem cell differentiation and metabolism.</p><p><strong>Results: </strong>EGFR inhibition improved bone callus formation and quality, increased cartilage callus, and upregulated bone formation markers. Gefitinib enhanced oxidative phosphorylation and fatty acid oxidation, counteracting negative effects from lipid-reduced serum on osteoblastic differentiation of periosteal stem cell. SOX9 overexpression reduced the benefits of EGFR inhibition.</p><p><strong>Conclusion: </strong>Gefitinib enhances bone fracture healing by modulating lipid metabolism through SOX9, suggesting its potential as a therapeutic agent for improving fracture outcomes.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1394-1413"},"PeriodicalIF":1.8000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042003/pdf/","citationCount":"0","resultStr":"{\"title\":\"Gefitinib Facilitates Bone Fracture Healing <i>via</i> Inhibition of the EGFR Pathway and Counteracting SOX9-driven Bone Metabolic Reprogramming.\",\"authors\":\"Ning Xu, Gongwu Yuan, Wenbo Zeng, Ximing Liu, M A Wan, Suyang Xu, Yikang Bi, Hai Hu, Yafeng Xu, Shenghui Lan\",\"doi\":\"10.21873/invivo.13942\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>To investigate the role of epidermal growth factor receptor (EGFR) inhibition in enhancing bone fracture healing by modulating box transcription factor 9 (SOX9) and bone metabolism.</p><p><strong>Materials and methods: </strong>A rat femoral fracture model was used. Techniques included histological analysis, X-ray scoring, micro-computed tomography, immunohistochemistry, and biomechanical testing. Serum markers were analyzed with enzyme-linked immunosorbent assay, while quantitative real-time polymerase chain reaction and western blotting assessed molecular pathways. Metabolic changes were measured using a Seahorse analyzer. An EGFR inhibitor, gefitinib, was used to examine its impact on periosteal stem cell differentiation and metabolism.</p><p><strong>Results: </strong>EGFR inhibition improved bone callus formation and quality, increased cartilage callus, and upregulated bone formation markers. Gefitinib enhanced oxidative phosphorylation and fatty acid oxidation, counteracting negative effects from lipid-reduced serum on osteoblastic differentiation of periosteal stem cell. SOX9 overexpression reduced the benefits of EGFR inhibition.</p><p><strong>Conclusion: </strong>Gefitinib enhances bone fracture healing by modulating lipid metabolism through SOX9, suggesting its potential as a therapeutic agent for improving fracture outcomes.</p>\",\"PeriodicalId\":13364,\"journal\":{\"name\":\"In vivo\",\"volume\":\"39 3\",\"pages\":\"1394-1413\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042003/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"In vivo\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21873/invivo.13942\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"In vivo","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/invivo.13942","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Gefitinib Facilitates Bone Fracture Healing via Inhibition of the EGFR Pathway and Counteracting SOX9-driven Bone Metabolic Reprogramming.
Background/aim: To investigate the role of epidermal growth factor receptor (EGFR) inhibition in enhancing bone fracture healing by modulating box transcription factor 9 (SOX9) and bone metabolism.
Materials and methods: A rat femoral fracture model was used. Techniques included histological analysis, X-ray scoring, micro-computed tomography, immunohistochemistry, and biomechanical testing. Serum markers were analyzed with enzyme-linked immunosorbent assay, while quantitative real-time polymerase chain reaction and western blotting assessed molecular pathways. Metabolic changes were measured using a Seahorse analyzer. An EGFR inhibitor, gefitinib, was used to examine its impact on periosteal stem cell differentiation and metabolism.
Results: EGFR inhibition improved bone callus formation and quality, increased cartilage callus, and upregulated bone formation markers. Gefitinib enhanced oxidative phosphorylation and fatty acid oxidation, counteracting negative effects from lipid-reduced serum on osteoblastic differentiation of periosteal stem cell. SOX9 overexpression reduced the benefits of EGFR inhibition.
Conclusion: Gefitinib enhances bone fracture healing by modulating lipid metabolism through SOX9, suggesting its potential as a therapeutic agent for improving fracture outcomes.
期刊介绍：
IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management.
The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.
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