"Cellular Modulation of Growth Plate Regulatory Signals"
We are interested in how bones grow. More precisely, we want to understand the molecular and cellular mechanisms that control mammalian skeletal development, especially those involved in linear bone growth. Skeletal growth is primarily responsible for the final form of adult mammals. This is achieved for most bones through the generation of cartilage models that serve as a templates for bone growth, a process known as endochondral ossification. Once the embryonic bone is formed, endochondral ossification occurs near the ends of bones in so called growth plates .
The growth plate is a dynamic structure with a leading edge where new cells arise through mitosis, intermediate zones where terminally differentiatng cells synthesize matrix and facilitate its maturation into a functional template and a trailing edge where the template is degraded and replaced by bone. The synthesis of template, chondrogenesis, drives this process to a large extent.
A large number of genes must be involved in regulating these events judging from the many inherited human disorders (the chondrodysplasias) manifesting defective bone growth, as well as, the many naturally occurring skeletal mutants in mice and other species. However, there must also be much redundancy considering the many man-made misexpression and knockout mouse mutants that exhibit no abnormalities of skeletal development despite disrupting expression of genes that influence basic cell functions such as mitosis and differentiation. Our goal is to understand what the critical genes are and how they work to control the proliferation, survival and terminal differentiation of growth plate chondrocytes. Our experimental approach utilizes a wide variety of biochemical, molecular genetic, immunologic, molecular biology and cell biology methods. It is hoped our results will provide insight into the fundamental biologic process of growth and also establish a rational basis for new therapies for patients with bone growth disorders.