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

Autor: Lees-Shepard JB; Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, Connecticut, USA., Flint K; Department of Orthodontics, University of Connecticut Health Center, Farmington, Connecticut, USA., Fisher M; Department of Orthodontics, University of Connecticut Health Center, Farmington, Connecticut, USA., Omi M; Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, Connecticut, USA., Richard K; Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, Connecticut, USA., Antony M; Department of Orthodontics, University of Connecticut Health Center, Farmington, Connecticut, USA., Chen PJ; Department of Orthodontics, University of Connecticut Health Center, Farmington, Connecticut, USA., Yadav S; Department of Orthodontics, University of Connecticut Health Center, Farmington, Connecticut, USA., Threadgill D; Department of Veterinary Pathology, Texas A&M University, College Station, Texas, USA.; Department of Molecular and Cellular Medicine, Texas A&M University, College Station, Texas, USA., Maihle NJ; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.; Department of Cell & Molecular Biology, University of Mississippi Medical Center, Jackson, Mississippi, USA., Dealy CN; Department of Orthodontics, University of Connecticut Health Center, Farmington, Connecticut, USA.; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.; Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA.; Department of Cell Biology, University of Connecticut Health Center, Farmington, CT, USA.
Jazyk: angličtina
Zdroj: Developmental dynamics : an official publication of the American Association of Anatomists [Dev Dyn] 2022 Jan; Vol. 251 (1), pp. 75-94. Date of Electronic Publication: 2021 Nov 27.
DOI: 10.1002/dvdy.438
Abstrakt: 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.
(© 2021 American Association for Anatomy.)
Databáze: MEDLINE
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