THE BIOLOGY OF THE GROWTH PLATE

Abstract

• Chondrocytes in the growth plate undergo a complex series of molecular, biochemical, and morphological changes during the process of differentiation. • Longitudinal growth depends on both proliferation and hypertrophy of chondrocytes in the growth plate. • Integrated growth factor signaling pathways control the key transition between proliferation and hypertrophy that is required for completion of the maturation process. • Terminal chondrocyte maturation is associated with programmed cell death and the secretion of matrix and other factors that promote matrix calcification and vascular invasion. • Systemic hormones interact with local growth factors and signaling pathways to influence the rate of growth and lead to closure of the growth plate. In order for paired human limbs to reach the same adult length and proportions, the longitudinal growth of the skeleton must be tightly regulated. The regulation of longitudinal growth at the growth plate occurs generally through the intimate interaction of circulating systemic hormones and locally produced peptide growth factors, the net result of which is to trigger changes in gene expression by growth plate chondrocytes. These molecular events lead to precisely orchestrated alterations in chondrocyte size, extracellular matrix components, secreted enzymes and growth factors, and receptor expression. The culmination of these events is calcification of the matrix, chondrocyte apoptosis, and completion of endochondral bone formation. This review will highlight some of the advances in genetics and cell biology in the past decade that have begun to illuminate some of the important regulatory mechanisms governing the biology of the growth plate. The growth plate can be divided into a series of anatomic zones that distinguish unique morphological and biochemical stages during the process of chondrocyte differentiation. In the resting zone, the ratio of extracellular matrix to cell volume is high and the cells are in a relatively quiescent state. In the proliferating …