Collaborative Research: Determining the Impacts of Lacunar-Canalicular Remodeling on Bone Fracture Toughness

合作研究：确定腔隙-小管重塑对骨折韧性的影响

• 批准号: 2120239
• 负责人: Chelsea Heveran
• 金额: $ 41.31万
• 依托单位: Montana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2120239&HistoricalAwards=false
• 关键词: Collaborative; Research; Determining; Impacts; Lacunar

This award will support research to study bone fragility in aging, a major unsolved problem. Over 40 percent of women and 25 percent of men over 60 will experience a fragility fracture. The purpose of this research is to improve our understanding of the origins of bone toughness and to test if the loss of bone toughness is explained by the health of bone cells called osteocytes. Osteocytes are strain-sensing cells embedded in bone. These cells are interconnected by an expansive porous network. Osteocytes can remove and replace (that is, remodel) bone tissue surrounding this expansive network. Therefore, osteocytes may have an important but overlooked role in maintaining bone quality, specifically toughness. Because osteocyte health declines in aging and disease, it is important to understand whether interrupting osteocyte health decreases bone toughness. This project will advance the understanding of how, where, and why the osteocyte remodels bone and the impacts of osteocyte bone remodeling on bone toughness. The investigators will recruit and train underrepresented graduate and undergraduate students in the completion of the work. This work will also involve underrepresented undergraduate and high school students in the research and will engage K-12 students and teachers in bone biomechanics and materials science outreach activities. This project partners several novel approaches to investigate the impacts of osteocyte lacunar-canalicular remodeling on bone quality and fracture toughness. First, finite element modeling, histology, and histomorphometry will be used to assess the fraction of osteocytes that are remodeling bone tissue and evaluate whether osteocyte bone remodeling is related to bone tissue strain. Second, Auger electron spectroscopy will be used to produce submicron-resolution maps of bone mineral and matrix composition near osteocyte lacunae. Contact resonance atomic force microscopy maps will deliver an assessment of how bone energy dissipation, which determines bone fracture toughness, varies at the submicrometer-scale. Third, a high dietary fat diet will be used as a novel platform to study how lacunar-canicular remodeling affects bone fracture toughness. These models exploit the detrimental effect of fat on osteocyte health to modulate lacunar-canicular remodeling activities. The key outcomes of the project are (1) the number and location of remodeling osteocytes and determination of whether lacunar-canicular remodeling is related to bone tissue strain, (2) bone composition and mechanical properties at a physiologically-relevant resolution near remodeling and non-remodeling osteocytes, and (3) determination of whether lacunar-canicular remodeling beneficially impacts bone fracture toughness. This project is jointly funded by the Biomechanics and Mechanobiology program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项将支持研究衰老的骨骼脆弱性，这是一个主要的未解决问题。超过40％的女性和60岁以上的男性将经历脆弱性骨折。这项研究的目的是提高我们对骨骼韧性起源的理解，并测试骨骼细胞的骨细胞健康是否丧失了骨细胞的健康。骨细胞是嵌入骨骼中的应变感应细胞。 这些细胞通过膨胀的多孔网络互连。骨细胞可以去除并替换（即重塑）围绕该膨胀网络的骨组织。 因此，骨细胞可能在保持骨骼质量（特别是韧性）中具有重要但忽视的作用。由于骨细胞健康的衰老和疾病下降，因此重要的是要了解中断骨细胞健康是否会降低骨骼韧性。该项目将促进对骨细胞重塑骨骼以及骨细胞骨重塑对骨骼韧性的影响的理解。调查人员将在完成工作后招募和培训代表性不足的研究生和本科生。这项工作还将涉及代表性不足的本科生和高中生参与研究，并将与K-12学生和老师参与骨生物力学和材料科学外展活动。该项目构成了几种新的方法，以研究骨细胞lacunar-囊状重塑对骨质质量和断裂韧性的影响。首先，有限元建模，组织学和组织形态计量学将用于评估重塑骨组织的骨细胞的比例，并评估骨细胞骨重塑是否与骨组织菌株有关。其次，螺旋钻电子光谱法将用于在骨细胞lacunae附近生成骨矿物质和基质组成的亚微米分辨率图。接触谐振原子力显微镜图将评估骨能量耗散（决定骨断裂韧性）在亚微米尺度上有所不同。第三，高饮食饮食将被用作一个新的平台，用于研究lacunar-划界重塑如何影响骨断裂韧性。这些模型利用了脂肪对骨细胞健康的有害作用，以调节lacunar-cannicular重塑活性。该项目的关键结果是（1）重塑骨细胞的数量和位置以及确定lacunar-循环 - 跨性重塑是否与骨骼组织应变相关，（2）在生理上相关的分辨率和非重塑和（3）的（3）确定（3）的骨组成和机械性能是否与生理相关的分辨率相关（3）影响骨断裂韧性。 该项目由生物力学和机械生物学计划和启发竞争性研究的既定计划共同资助（EPSCOR）。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛影响的评估来评估的评估。

项目成果

Osteocyte Remodeling of the Lacunar-Canalicular System: What’s in a Name?

• DOI: 10.1007/s11914-022-00766-3
• 发表时间: 2022-12
• 期刊: Current Osteoporosis Reports
• 影响因子: 4.3
• 作者: C. Heveran;J. Boerckel