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Roles of EGF Family of Growth Factors in Growth: Overview of Their Roles in Postnatal Growth and Development

Chapter

Abstract

Ligands of the epidermal growth factor receptor (EGF-R), known to be important for supporting embryonic tissue development particularly in the gut and brain, have also been implicated in regulating postnatal somatic growth. While optimal levels of both milk-borne and endogenous EGF-R ligands are important for supporting postnatal somatic growth through regulating gastrointestinal growth and maturation, supra-physiological levels of EGF-R ligands can cause retarded and disproportionate growth and alter body composition as they increase growth of epithelial tissues but decrease masses of muscle, fat, and bone. EGF-R ligands can exert influence on growth indirectly via regulating levels of insulin-like growth factor (IGF-I) and its binding proteins (IGFBPs); EGF-R ligands can also directly regulate bone growth and modeling, as they can enhance proliferation but suppress maturation of growth plate chondrocytes (for building a calcified cartilage scaffold for bone deposition) and osteoblasts (for depositing bone matrix), and promote formation and function of osteoclasts (for resorption of calcified cartilage or bone). In addition, EGF-R ligands, in particular amphiregulin, can themselves be regulated by parathyroid hormone (PTH), an important regulatory factor in bone modeling and remodeling. Finally, EGF-R ligands can regulate bone homeostasis by regulating pool of progenitor cells in the bone marrow through promoting their proliferation but suppressing differentiation of bone marrow mesenchymal stem cells.

Keywords

EGF family EGF-R or ErbB receptors Somatic growth Body composition IGF-I IGFBP Bone growth Growth plate Osteoblasts Osteoclasts Bone resorption Mesenchymal stem cells 

Abbreviations

AR

Amphiregulin

BMPs

Bone morphogenic proteins

BTC

Betacellulin

CFU-F

Colony-forming unit fibroblasts

EPR

Epiregulin

EGF

Epidermal growth factor

EGF-R

Epidermal growth factor receptor

ERK

Extracellular signal-regulated kinase

FGF

Fibroblast growth factor

GH

Growth hormone

HB-EGF

Heparin-binding epidermal growth factor

IGF

Insulin-like growth factor

IGFBPs

Insulin-like growth factor-binding proteins

MAP

Mitogen-activated protein

MAPK

Mitogen-activated protein kinase

M-CSF

Macrophage colony-stimulating factor

MMPs

Matrix metalloproteases

MSCs

Mesenchymal stem cells

NF

Nuclear factor

OPG

Osteoprotegerin

PTH

Parathyroid hormone

PTHrP

Parathyroid hormone-related peptide

RANK

Receptor activator of nuclear factor-κB

RANKL

Receptor activator of nuclear factor-κB ligand

TGF-α

Transforming growth factor-alpha

TNF-α

Tumor necrosis factor-alpha

Notes

Acknowledgments

Work from the author’s lab was supported in part by the Bone Growth Foundation (Australia) and project grants and fellowship from the Australia National Health and Medical Research Council (NHMRC).

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.School of Pharmacy and Medical SciencesSansom Institute for Health Research, University of South AustraliaAdelaideAustralia

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