Journal article
EGFR Signaling Is Required for Maintaining Adult Cartilage Homeostasis and Attenuating Osteoarthritis Progression
Journal of bone and mineral research, v 37(5), pp 1012-1023
09 Mar 2022
PMID: 35191092
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The uppermost superficial zone of articular cartilage is the first line of defense against the initiation of osteoarthritis (OA). We previously used Col2-Cre to demonstrate that epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, plays an essential role in maintaining superficial chondrocytes during articular cartilage development. Here, we showed that EGFR activity in the articular cartilage decreased as mice age. In mouse and human OA samples, EGFR activity was initially reduced at the superficial layer and then resurged in cell clusters within the middle and deep zone in late OA. To investigate the role of EGFR signaling in postnatal and adult cartilage, we constructed an inducible mouse model with cartilage-specific EGFR inactivation (Aggrecan-CreER Egfr(Wa5/flox), Egfr iCKO). EdU incorporation revealed that postnatal Egfr iCKO mice contained fewer slow-cycling cells than controls. EGFR deficiency induced at 3 months of age reduced cartilage thickness and diminished superficial chondrocytes, in parallel to alterations in lubricin production, cell proliferation, and survival. Furthermore, male Egfr iCKO mice developed much more severe OA phenotypes, including cartilage erosion, subchondral bone plate thickening, cartilage degeneration at the lateral site, and mechanical allodynia, after receiving destabilization of the medial meniscus (DMM) surgery. Similar OA phenotypes were also observed in female iCKO mice. Moreover, tamoxifen injections of iCKO mice at 1 month post-surgery accelerated OA development 2 months later. In summary, our data demonstrated that chondrogenic EGFR signaling maintains postnatal slow-cycling cells and plays a critical role in adult cartilage homeostasis and OA progression. (c) 2022 American Society for Bone and Mineral Research (ASBMR).
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Details
- Title
- EGFR Signaling Is Required for Maintaining Adult Cartilage Homeostasis and Attenuating Osteoarthritis Progression
- Creators
- Yulong Wei - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Xiaoyuan Ma - University of PennsylvaniaHao Sun - University of PennsylvaniaTao Gui - University of PennsylvaniaJun Li - University of PennsylvaniaLutian Yao - University of PennsylvaniaLeilei Zhong - University of PennsylvaniaWei Yu - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Biao Han - Drexel UniversityCharles L. Nelson - University of PennsylvaniaLin Han - Drexel UniversityFrank Beier - Western UniversityMotomi Enomoto-Iwamoto - University of Maryland, BaltimoreJaimo Ahn - University of PennsylvaniaLing Qin - Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, 311A Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA
- Publication Details
- Journal of bone and mineral research, v 37(5), pp 1012-1023
- Publisher
- Wiley
- Number of pages
- 12
- Grant note
- R01AG067698; R01AR074490; P30AR069619 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000766130600001
- Scopus ID
- 2-s2.0-85125867147
- Other Identifier
- 991019168197704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Endocrinology & Metabolism