The goal of this application is to provide Yale Medical School investigators that share an interest in bone biology with an instrument that will propel research in a necessary way. The instrument is a peripheral Quantitative Computerized Tomography (pQCT) that provides precise and rapid quantitative information about trabecular and cortical bone density in small live animals, such as mice and rats. Yale is the home of a large number of investigators who share an interest in bone biology, and who are more and more frequently translating their approach in vivo using rats and genetically engineered mice. These investigators are either well established, or new in the field of bone biology, and are associated with several departments at Yale School of Medicine, including the departments of Cell Biology, Immunobiology, Medicine, Orthopaedic Surgery, Pathology, Pharmacology, Comparative Medicine and Plastic Surgery. Yet, despite its large number of bone biologists, Yale is not equipped with state-of-the-art equipment to determine the quantity and the quality of bone in small animals that are used as experimental models.
The specific aim of this application is therefore to acquire a pQCT to determine the trabecular and cortical bone density in live animals treated with a bone anabolic or anti catabolic drug/hormone, to assess the efficacy of the treatment. A pQCT can determine the trabecular and cortical bone density in live mice genetically engineered to either over express, or lack a specific gene that plays a central role in bone development, repair or homeostasis. A pQCT can also determine bone density in excised bones. The principal investigator and the key personnel of this application, together, are committed to further our understanding of the biology of bone with a common goal that is to prevent and repair bone loss, and treat diseases in which bone development and/or mass is altered. The projects proposed by the applicants focus on the differentiation and the activation of multinucleate osteoclasts, the cells that resorb bone (Drs Horne, Kyriakides and Vignery) and of osteoblasts, the cells that make bone, with specific emphasis on FGF and WNT downstream signaling (Drs Schlessinger, Gundberg, Horvath and Wu). In addition, the mechanism by which PTH activates osteoblasts is addressed by Dr Bennett. Together, these investigators cover large and complementary research fields in bone biology that bring together departments that have different, yet complementary conceptual approaches, and thereby enrich the field of bone biology. ? ? ?
