Introduction

Cartilage is the template on which much of the skeletal bone is formed, both during the primary ossification processes of embryonic and fetal development, and during pre- and post-natal longitudinal skeletal growth as a result of epiphyseal chondrogenesis. Three main classes of growth factors have been associated with these processes, the fibroblast growth factors (FGFs), the insulin-like growth factors -I and -II (IGFs-I and -II), and members of the transforming growth factor-β (TGF-β) family, including TGF-βs 1, 2 and 3, and bone morphogenetic proteins 2B and 3. This paper reviews three likely roles of these growth factors in the regulation of limb and skeletal formation, and in the subsequent processes of epiphyseal chondrogenesis.

Limb development

Formation of the limb buds and the subsequent skeletal structure of the limbs have been well studied in the chick embyro, and are now thought to be tightly controlled by peptide growth factors. The limb buds first develop as a thickening of the body wall mesenchyme, the surface ectoderm of which is induced by the underlying mesenchyme to form a specialized structure called the apical ectodermal ridge. The mesenchyme beneath the apical ectodermal ridge is maintained in an undifferentiated, rapidly proliferating state and enables outgrowth of the limb to occur. Limb outgrowth is promptly arrested following removal of the apical ectodermal ridge. As mesenchyme moves distally to the progress zone, so it undergoes a condensation and morphogenic change to become cartilage. Sub-periosteal bone then develops on the surface of the cartilage immediately below the perichondrium to give rise to primary ossification structures.