Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment
Osteoarthritis (OA) is a leading cause of physical disability among aging populations, with no available drugs able to efficiently restore the balance between cartilage matrix synthesis and degradation. Also, OA has not been accurately classified into subpopulations, hindering the development toward...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418302044 |
| _version_ | 1828768116149059584 |
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| author | Heng Sun Yan Wu Zongyou Pan Dongsheng Yu Pengfei Chen Xiaoan Zhang Haoyu Wu Xiaolei Zhang Chengrui An Yishan Chen Tian Qin Xiaoyue Lei Chunhui Yuan Shufang Zhang Weiguo Zou Hongwei Ouyang |
| author_facet | Heng Sun Yan Wu Zongyou Pan Dongsheng Yu Pengfei Chen Xiaoan Zhang Haoyu Wu Xiaolei Zhang Chengrui An Yishan Chen Tian Qin Xiaoyue Lei Chunhui Yuan Shufang Zhang Weiguo Zou Hongwei Ouyang |
| author_sort | Heng Sun |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a leading cause of physical disability among aging populations, with no available drugs able to efficiently restore the balance between cartilage matrix synthesis and degradation. Also, OA has not been accurately classified into subpopulations, hindering the development toward personalized precision medicine.In the present study, we identified a subpopulation of OA patients displaying high activation level of epidermal growth factor receptor (EGFR). With Col2a1-creERT2; Egfrf/f mice, it was found that the activation of EGFR, indicated by EGFR phosphorylation (pEGFR), led to the destruction of joints. Excitingly, EGFR inhibition prohibited cartilage matrix degeneration and promoted cartilage regeneration. The Food and Drug Administration (FDA)-approved drug gefitinib could efficiently inhibit EGFR functions in OA joints and restore cartilage structure and function in the mouse model as well as the clinical case report.Overall, our findings suggested the concept of the EGFR activated OA subpopulation and illustrated the mechanism of EGFR signaling in regulating cartilage homeostasis. Gefitinib could be a promising disease-modifying drug for this OA subpopulation treatment. Keywords: Osteoarthritis, Disease subpopulation, Epidermal growth factor receptor, Gefitinib |
| first_indexed | 2024-12-11T07:40:52Z |
| format | Article |
| id | doaj.art-2ecc03daec174c0aa028d94037e58211 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T07:40:52Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-2ecc03daec174c0aa028d94037e582112022-12-22T01:15:34ZengElsevierEBioMedicine2352-39642018-06-0132223233Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation TreatmentHeng Sun0Yan Wu1Zongyou Pan2Dongsheng Yu3Pengfei Chen4Xiaoan Zhang5Haoyu Wu6Xiaolei Zhang7Chengrui An8Yishan Chen9Tian Qin10Xiaoyue Lei11Chunhui Yuan12Shufang Zhang13Weiguo Zou14Hongwei Ouyang15Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China; Department of Orthopeadics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China; Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China; Department of Orthopaedics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, ChinaDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310058, China; Corresponding author at: Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.Osteoarthritis (OA) is a leading cause of physical disability among aging populations, with no available drugs able to efficiently restore the balance between cartilage matrix synthesis and degradation. Also, OA has not been accurately classified into subpopulations, hindering the development toward personalized precision medicine.In the present study, we identified a subpopulation of OA patients displaying high activation level of epidermal growth factor receptor (EGFR). With Col2a1-creERT2; Egfrf/f mice, it was found that the activation of EGFR, indicated by EGFR phosphorylation (pEGFR), led to the destruction of joints. Excitingly, EGFR inhibition prohibited cartilage matrix degeneration and promoted cartilage regeneration. The Food and Drug Administration (FDA)-approved drug gefitinib could efficiently inhibit EGFR functions in OA joints and restore cartilage structure and function in the mouse model as well as the clinical case report.Overall, our findings suggested the concept of the EGFR activated OA subpopulation and illustrated the mechanism of EGFR signaling in regulating cartilage homeostasis. Gefitinib could be a promising disease-modifying drug for this OA subpopulation treatment. Keywords: Osteoarthritis, Disease subpopulation, Epidermal growth factor receptor, Gefitinibhttp://www.sciencedirect.com/science/article/pii/S2352396418302044 |
| spellingShingle | Heng Sun Yan Wu Zongyou Pan Dongsheng Yu Pengfei Chen Xiaoan Zhang Haoyu Wu Xiaolei Zhang Chengrui An Yishan Chen Tian Qin Xiaoyue Lei Chunhui Yuan Shufang Zhang Weiguo Zou Hongwei Ouyang Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment EBioMedicine |
| title | Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment |
| title_full | Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment |
| title_fullStr | Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment |
| title_full_unstemmed | Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment |
| title_short | Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment |
| title_sort | gefitinib for epidermal growth factor receptor activated osteoarthritis subpopulation treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418302044 |
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