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Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein\u20102 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross\u2010talk between EGFR and BMP2 signals in developing and adult growth plates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using in vivo mouse models of conditional cartilage\u2010targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR\u2010deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2\u2010deficient growth plates. EGFR\u2010deficient 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cross\u2010talk 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\u2010talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.438","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T07:34:09Z","timestamp":1636788849000},"page":"193-212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cross\u2010talk between <scp>EGFR<\/scp> and <scp>BMP<\/scp> signals regulates chondrocyte maturation during endochondral ossification"],"prefix":"10.1002","volume":"251","author":[{"given":"John B.","family":"Lees\u2010Shepard","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences University of Connecticut Health Center  Farmington Connecticut 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