Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment
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
Affiliations
Heng Sun
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Yan Wu
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; 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, China
Zongyou Pan
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Dongsheng Yu
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; 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, China
Pengfei Chen
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Xiaoan Zhang
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Haoyu Wu
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Xiaolei Zhang
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; 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, China
Chengrui An
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Yishan Chen
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Tian Qin
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Xiaoyue Lei
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Chunhui Yuan
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Shufang Zhang
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; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China
Weiguo Zou
State 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, China
Hongwei Ouyang
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; 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, Gefitinib
