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

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.