Autocrine, paracrine, and hormonal signals involved in growth plate chondrocyte differentiation

Longitudinal bone growth depends upon intricate steps in the metabolism and differentiation of epiphyseal growth plate chondrocytes. These steps involve cell proliferation followed by the synthesis of gene products that are characteristic of the subsequent stages of differentiation. Until recently, the major control of growth plate metabolism was thought to reside with systemic hormones, principally growth hormone. However, it is now apparent that locally produced peptide growth factors play important autocrine and paracrine roles in normal growth plate physiology. Investigations with cultured chondrocytes have demonstrated the importance of the peptide growth factors insulin-like growth factor-I, transforming growth factor-beta, and basic fibroblast growth factor for cell proliferation, extracellular matrix biosynthesis, and changes in morphology associated with the progressive stages of chondrocyte differentiation. All three of these factors have been shown to be present in specific zones of the epiphyseal growth plate. A preliminary map of the epiphyseal growth plate is proposed, which delineates the site and mode of action of systemic and locally produced factors involved in longitudinal bone growth.