Cross-talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification

John B. Lees-Shepard, Kaitlyn Flint, Melanie Fisher, Minoru Omi, Kelsey Richard, Michelle Antony, Po Jung Chen, Sumit Yadav, David Threadgill, Nita J. Maihle, Caroline N. Dealy

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Progressive maturation of growth plate chondrocytes drives long bone growth during endochondral ossification. Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein-2 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross-talk between EGFR and BMP2 signals in developing and adult growth plates. Results: Using in vivo mouse models of conditional cartilage-targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR-deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2-deficient growth plates. EGFR-deficient chondrocytes displayed increased BMP signal activation in vitro, accompanied by increased expression of IHH, COL10A1, and RUNX2. Hypertrophic differentiation and BMP signal activation were suppressed in normal chondrocyte cultures treated with the EGFR ligand betacellulin, effects that were partially blocked by simultaneous treatment with BMP2 or a chemical EGFR antagonist. Conclusions: Cross-talk between EGFR and BMP2 signals occurs during chondrocyte maturation. In the reserve and prehypertrophic zones, BMP2 signals unilaterally suppress EGFR activity; in the hypertrophic zone, EGFR and BMP2 signals repress each other. This cross-talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.

Original languageEnglish
Pages (from-to)75-94
Number of pages20
JournalDevelopmental Dynamics
Volume251
Issue number1
DOIs
Publication statusPublished - 01-2022

All Science Journal Classification (ASJC) codes

  • Developmental Biology

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