Converting a differentiation cascade into longitudinal growth: stereology and analysis of transgenic animals as tools for understanding growth plate function

Abstract

In the past decade, the study of chondrocytic differentiation within the growth plates at the ends of long bones has been approached from multiple perspectives. The spatial organization of growth plate columns with proliferating cells proximally and fully differentiated hypertrophic cells distally represents the temporal maturation of any one chondrocyte. Therefore the growth plate is a particularly powerful way to follow the chondrocytic differentiation cascade over time. Through stereological analyses of growth plate cellular function, the basics of the kinetics of the proliferative and hypertrophic populations have been studied, including the quantitative differential contributions of cellular proliferation, volume increase, and matrix production to longitudinal growth in growth plates growing at different rates. Analysis of transgenic animals has provided a powerful tool to add an understanding of the transitions between differentiation states of chondrocytes and the systemic, paracrine, and autocrine regulators that are critical at these transitions. As the sophistication of the transgenic constructs increases, it becomes critical to sort out the potential differences in regulatory pathways in prenatal versus postnatal environments, and also to recognize several caveats when results of analyses in one species are generalized to multiple species, including humans.