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Updated: Aug 21, 2026
Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification
Published on: December 3, 2016
Epidermal growth factor receptor-deficient mice have delayed primary endochondral ossification because of defective
Ke Wang1, Hiroaki Yamamoto, Jennie R Chin
1Department of Medicine, University of California, San Francisco, CA 94143, USA.
Abstract:
The epidermal growth factor receptor (EGFR) and its ligands function in diverse cellular functions including cell proliferation, differentiation, motility, and survival. EGFR signaling is important for the development of many tissues, including skin, lungs, intestines, and the craniofacial skeleton. We have now determined the role of EGFR signaling in endochondral ossification. We analyzed long bone development in EGFR-deficient mice. EGFR deficiency caused delayed primary ossification of the cartilage anlage and delayed osteoclast and osteoblast recruitment. Ossification of the growth plates was also abnormal resulting in an expanded area of growth plate hypertrophic cartilage and few bony trabeculae. The delayed osteoclast recruitment was not because of inadequate expression of matrix metalloproteinases, including matrix metalloproteinase-9, which have previously been shown to be important for osteoclast recruitment. EGFR was expressed by osteoclasts, suggesting that EGFR ligands may act directly to affect the formation and/or function of these cells. EGFR signaling regulated osteoclast formation. Inhibition of EGFR tyrosine kinase activity decreased the generation of osteoclasts from cultured bone marrow cells.
Insights
Epidermal growth factor receptor (EGFR) signaling is crucial for bone development. EGFR deficiency in mice led to delayed ossification and abnormal growth plate development, impacting osteoclast formation.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) signaling regulates critical cellular functions like proliferation, differentiation, motility, and survival.
- EGFR signaling is vital for the development of various tissues, including skin, lungs, intestines, and the craniofacial skeleton.
Purpose of the Study:
- To elucidate the role of EGFR signaling in endochondral ossification and long bone development.
Main Methods:
- Analysis of long bone development in EGFR-deficient mice.
- Assessment of osteoclast and osteoblast recruitment and activity.
- Investigation of matrix metalloproteinase expression.
- Evaluation of EGFR expression in osteoclasts.
- Inhibition of EGFR tyrosine kinase activity in cultured bone marrow cells.
Main Results:
- EGFR deficiency resulted in delayed primary ossification of the cartilage anlage.
- Osteoclast and osteoblast recruitment was delayed in EGFR-deficient mice.
- Growth plate ossification was abnormal, characterized by expanded hypertrophic cartilage and reduced bony trabeculae.
- Delayed osteoclast recruitment was not linked to insufficient matrix metalloproteinase-9 expression.
- EGFR expression in osteoclasts suggests direct ligand action on osteoclast formation and/or function.
- Inhibition of EGFR tyrosine kinase activity reduced osteoclast generation from bone marrow cells.
Conclusions:
- EGFR signaling plays a significant role in regulating endochondral ossification and long bone development.
- EGFR signaling directly influences osteoclast formation and/or function.
- Targeting EGFR signaling may offer therapeutic potential for bone development disorders.
