Meeting Abstract

P3-29   -   Regulation of differential growth rates of long bones by insulin-like growth factors Marquez, AP*; McKenna, KM; Cooper, KL; University of California, San Diego a8marque@ucsd.edu

The mammalian skeletal system offers a unique opportunity to understand evolution of complex multicellular organisms. All long bones share a common developmental process, and yet some bones grow extraordinarily large while others seem to grow little at all. In humans, for example, bones span an order of magnitude from the shortest toe bones to the long bones that make up the arms and legs, and bones evolved independently of one another to diversify mammal skeletons. Such differences hint at a level of developmental autonomy, or modularity, that would allow bones to grow at different rates and for different durations of time. Regardless of individualized growth rate, all long bones grow by a process of endochondral ossification centered on activities of chondrocytes in the growth cartilage proliferating and undergoing massive cellular enlargement. Interestingly, enlargement and proliferation may be regulated by local insulin-like growth factors, IGF-1 and IGF-2, respectively. The aim of this study is to obtain insight into how IGF-1 and IGF-2 contribute to the differential regulation of the cellular and molecular mechanisms of long bone growth. Using conditional knockout mice for IGF-1 and IGF-2, we demonstrate their relative contributions to skeletal proportions. Additionally, we identify a possible mechanism for the bifurcation of the insulin signaling pathway that accounts for these differences in the regulation of cell behaviors in the growth plate.