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过程中骨骼脆性的研究，这是一个尚未解决的主要问题。超过40%的60岁以上的女性和25%的男性将经历脆性骨折。这项研究的目的是为了提高我们对骨骼韧性起源的理解，并测试骨骼韧性的丧失是否可以通过称为骨细胞的骨细胞的健康来解释。骨细胞是嵌入在骨骼中的应变敏感细胞。这些细胞通过一个扩张的多孔网络相互连接。骨细胞可以移除和替换(也就是重塑)这个扩张网络周围的骨组织。因此，骨细胞在维持骨骼质量，特别是韧性方面可能具有重要但被忽视的作用。由于骨细胞健康会随着年龄和疾病的增加而下降，因此了解干扰骨细胞健康是否会降低骨的韧性是很重要的。这个项目将促进对骨细胞如何、在哪里和为什么重塑骨骼以及骨细胞骨重塑对骨骼韧性的影响的理解。调查人员将招聘和培训任职人数不足的研究生和本科生，以完成工作。这项工作还将使未被充分代表的本科生和高中生参与研究，并将使K-12学生和教师参与骨生物力学和材料科学推广活动。该项目合作了几种新的方法来研究骨细胞腔隙-管状重塑对骨质量和骨折韧性的影响。首先，将使用有限元建模、组织学和组织形态计量学来评估骨组织改建的骨细胞比例，并评估骨细胞骨改建是否与骨组织应变有关。其次，俄歇电子能谱将用于制作骨细胞陷窝附近的骨矿物质和基质成分的亚微米分辨率地图。接触共振原子力显微镜地图将提供对决定骨骼断裂韧性的骨骼能量耗散在亚微米尺度上如何变化的评估。第三，高脂肪饮食将被用作研究腔隙-骨管重塑如何影响骨断裂韧性的新平台。这些模型利用脂肪对骨细胞健康的有害影响来调节腔隙-小管重塑活动。该项目的关键成果是(1)重建骨细胞的数量和位置，以及确定腔隙-管重建是否与骨组织应变有关，(2)重建和非重建骨细胞附近生理相关的骨成分和力学性能，以及(3)腔隙-管重建是否有益于骨断裂韧性的确定。该项目由生物力学和机械生物学计划和既定的激励竞争性研究计划(EPSCoR)共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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