EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation

Haoruo Jia, Xiaoyuan Ma, Wei Tong, Basak Doyran, Zeyang Sun, Luqiang Wang, Xianrong Zhang, Yilu Zhou, Farid Badar, Abhishek Chandra, X. Lucas Lu, Yang Xia, Lin Han, Motomi Enomoto-Iwamoto, Ling Qina

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)14360-14365
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number50
DOIs
StatePublished - Dec 13 2016

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Keywords

  • Articular cartilage
  • Chondrocyte
  • EGFR
  • Lubrication
  • Osteoarthritis

ASJC Scopus subject areas

  • General

Cite this

Jia, H., Ma, X., Tong, W., Doyran, B., Sun, Z., Wang, L., Zhang, X., Zhou, Y., Badar, F., Chandra, A., Lucas Lu, X., Xia, Y., Han, L., Enomoto-Iwamoto, M., & Qina, L. (2016). EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation. Proceedings of the National Academy of Sciences of the United States of America, 113(50), 14360-14365. https://doi.org/10.1073/pnas.1608938113