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描述(由申请者提供)：本申请的目标是为耶鲁医学院对骨骼生物学有共同兴趣的研究人员提供一种仪器，以必要的方式推动研究。该仪器是一种外围定量计算机断层扫描(PQCT)，可提供有关小动物(如小鼠和大鼠)骨小梁和皮质骨密度的准确和快速的定量信息。耶鲁大学是大量对骨骼生物学感兴趣的研究人员的故乡，他们越来越频繁地使用大鼠和基因工程小鼠在体内转换他们的方法。这些研究人员要么是骨生物学领域的老手，要么是新手，与耶鲁医学院的几个系有联系，包括细胞生物学、免疫生物学、医学、整形外科、病理学、药理学、比较医学和整形外科。然而，尽管有大量的骨骼生物学家，耶鲁大学并没有配备最先进的设备来确定用作实验模型的小动物的骨骼的数量和质量。因此，这项应用的具体目的是获得一种pQCT，以测定经骨合成代谢或抗分解代谢药物/激素治疗的活体动物的骨小梁和皮质骨密度，以评估该治疗的疗效。PQCT可以确定活体小鼠的骨小梁和皮质骨密度，通过基因工程，小鼠的骨小梁和皮质骨密度要么过度表达，要么缺乏在骨骼发育、修复或稳态中发挥核心作用的特定基因。PQCT还可以确定切除骨中的骨密度。这项应用的主要研究人员和关键人员共同致力于加深我们对骨生物学的理解，共同的目标是预防和修复骨丢失，并治疗骨发育和/或骨质量改变的疾病。申请者提出的项目侧重于多核破骨细胞的分化和激活，即吸收骨的细胞(DRS Horne、Kyriakides和Vignery)和成骨细胞(构成骨的细胞)，并特别强调成纤维细胞生长因子和WNT下游信号(DRS Schless、Gundberg、Horvath和Wu)。此外，贝内特博士还阐述了甲状旁腺素激活成骨细胞的机制。这些研究人员共同涵盖了骨生物学中广泛和互补的研究领域，将拥有不同但互补的概念方法的部门聚集在一起，从而丰富了骨生物学领域。

DESCRIPTION (provided by applicant): 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.