Journal article
EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation
Proceedings of the National Academy of Sciences - PNAS, v 113(50), pp 14360-14365
13 Dec 2016
PMCID: PMC5167216
PMID: 27911782
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox). These mice developed early cartilage degeneration at 6 mo of age. By 2 mo of age, although their gross cartilage morphology appears normal, CKO mice had a drastically reduced number of superficial chondrocytes and decreased lubricant secretion at the surface. Using superficial chondrocyte and cartilage explant cultures, we demonstrated that EGFR signaling is critical for maintaining the number and properties of superficial chondrocytes, promoting chondrogenic proteoglycan 4 (Prg4) expression, and stimulating the lubrication function of the cartilage surface. In addition, EGFR deficiency greatly disorganized collagen fibrils in articular cartilage and strikingly reduced cartilage surface modulus. After surgical induction of OA at 3 mo of age, CKO mice quickly developed the most severe OA phenotype, including a complete loss of cartilage, extremely high surface modulus, subchondral bone plate thickening, and elevated joint pain. Taken together, our studies establish EGFR signaling as an important regulator of the superficial layer during articular cartilage development and OA initiation.
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Details
- Title
- EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation
- Creators
- Haoruo Jia - University of PennsylvaniaXiaoyuan Ma - University of PennsylvaniaWei Tong - University of PennsylvaniaBasak Doyran - Drexel UniversityZeyang Sun - University of PennsylvaniaLuqiang Wang - University of PennsylvaniaXianrong Zhang - University of PennsylvaniaYilu Zhou - University of DelawareFarid Badar - Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309.Abhishek Chandra - University of PennsylvaniaX Lucas Lu - University of DelawareYang Xia - Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309.Lin Han - Drexel UniversityMotomi Enomoto-Iwamoto - University of PennsylvaniaLing Qin - University of Pennsylvania
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 113(50), pp 14360-14365
- Publisher
- PNAS
- Grant note
- R01 AR066098 / NIAMS NIH HHS R21 AR066824 / NIAMS NIH HHS R01 AR052353 / NIAMS NIH HHS P30 AR069619 / NIAMS NIH HHS R01 DK095803 / NIDDK NIH HHS R03 AR060991 / NIAMS NIH HHS R01 AR069047 / NIAMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000389696700062
- Scopus ID
- 2-s2.0-85006098488
- Other Identifier
- 991019168521704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Rheumatology