Black Bear Bone Mechanics

描述(申请人提供)：骨质疏松症是一种以骨量减少和骨组织结构恶化为特征的疾病，导致骨骼脆性和骨折风险增加。造成皮质骨结构恶化的主要因素是骨重建引起的孔隙率增加。因此，骨骼的强度和刚度会降低。对于长时间卧床、固定和太空飞行，骨的废用性萎缩是普遍存在的，当恢复正常的骨负荷时，会增加骨折的风险。废用性骨质减少症发生在许多动物身上，包括大鼠、公鸡、冬眠的地面松鼠、绵羊、狗、猴子和人类。相反，黑熊可能不会像其他动物那样，在长时间的不使用(即冬眠)期间出现骨量减少。在冬眠期间，破骨细胞的吸收增加，就像在其他动物身上一样。然而，成骨细胞的形成水平保持正常，这是熊特有的代谢性骨骼特征。此外，与其他动物相比，黑熊可能有一种机制，可以更快、更完整地从废弃状态中恢复骨骼。因此，我们假设黑熊最大限度地减少了因每年一次的废弃而导致的骨材料性能的退化，因为它们在废弃期间保持正常的骨形成，并在重新动员期间快速而完全地恢复骨量。该项目的总体目标是了解每年停用一段时间对骨机械性能、组织学特征和矿物成分的影响，以及在再动员过程中可能涉及的骨恢复的生物学机制。该项目的目标是(1)量化黑熊骨骼力学性能、矿物质含量和组织学特征随年龄的变化，以及(2)量化黑熊血清对体外培养的成骨细胞机械刺激的细胞内钙信号的影响。这将使用猎杀的熊的骨组织和从活熊收集的血清来完成，这些血清将用于成骨细胞的体外实验。拟议研究的长期影响包括了解废用性骨质疏松症的生物学机制，以及在治疗和预防骨质疏松症方面的进展，包括开发新的药物疗法。此外，本研究计划旨在培养本科生在生物学研究的实验设计、实验方法和数据分析方面的基本技能。

DESCRIPTION (provided by applicant): Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility and increased fracture risk. The major factor contributing to the structural deterioration of cortical bone is increased porosity caused by bone remodeling. Consequently, the strength and stiffness of bones are reduced. For prolonged bed rest, immobilization and space flight, disuse atrophy of bone is prevalent and increases fracture risk when normal bone loading is resumed. Disuse osteopenia occurs in many animals including rats, roosters, hibernating ground squirrels, sheep, dogs, monkeys and humans. On the contrary, black bears may not develop osteopenia during long periods of disuse (i.e., hibernation) to the extent that other animals do. During hibernation, osteoclastic resorption increases as it does in other animals. However, osteoblastic formation levels remain normal, a metabolic bone feature unique to bears. Additionally, black bears may have a mechanism for more rapid and complete bone recovery from disuse than other animals do. Therefore, we hypothesize that black bears minimize the degradation of bone material properties, which result from annual periods of disuse, because they maintain normal bone formation during disuse and make a rapid and complete recovery of bone mass during remobilization. The overall objective of this project is to understand the effects of annual periods of disuse on bone mechanical properties, histologic features, and mineral composition, and the biological mechanisms that may be involved in bone recovery during remobilization. The goals of the proposed project are (1) to quantify age-related changes in black bear bone mechanical properties, mineral content, and histologic features, and (2) to quantify the effects of black bear serum on mechanically stimulated intracellular calcium signaling in osteoblastic cells in vitro. This will be done with bone tissue from hunter-killed bears, and serum collected from live bears, which will be used for in vitro experiments with osteoblastic cells. The long-term impact of the proposed research includes an understanding of the biological mechanisms involved in disuse osteoporosis and advances in the treatment and prevention of osteoporosis, including the development of novel pharmaceutical therapies. Additionally, this research program is designed to train undergraduate students in the basic skills of experimental design, experimental methods, and data analysis for biological research.