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

基本信息

  • 批准号:
    2120230
  • 负责人:
  • 金额:
    $ 28.08万
  • 依托单位:
  • 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

项目摘要

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的骨脆弱性,这是一个尚未解决的重大问题。超过40%的女性和25%的60岁以上的男性会经历脆性骨折。这项研究的目的是提高我们对骨韧性起源的理解,并测试骨韧性的丧失是否可以由称为骨细胞的骨细胞的健康来解释。骨细胞是嵌入骨中的应变敏感细胞。 这些细胞通过一个膨胀的多孔网络相互连接。骨细胞可以移除和替换(即重塑)这个扩张网络周围的骨组织。 因此,骨细胞在维持骨质量,特别是韧性方面可能具有重要但被忽视的作用。由于骨细胞健康在衰老和疾病中下降,因此了解中断骨细胞健康是否会降低骨骼韧性非常重要。这个项目将促进了解骨细胞如何,在哪里,为什么重塑骨和骨细胞骨重塑对骨韧性的影响。调查人员将招募和培训代表性不足的研究生和本科生完成这项工作。这项工作还将涉及代表性不足的本科生和高中生的研究,并将从事K-12学生和教师在骨生物力学和材料科学的推广活动。本项目合作了几种新的方法来研究骨细胞腔隙-小管重建对骨质量和断裂韧性的影响。首先,将使用有限元建模、组织学和组织形态计量学来评估重塑骨组织的骨细胞的分数,并评价骨细胞骨重塑是否与骨组织应变相关。第二,俄歇电子能谱将用于产生骨矿物质和骨细胞陷窝附近的基质成分的亚微米分辨率图。接触共振原子力显微镜图将提供一个评估如何骨能量耗散,这决定了骨断裂韧性,在亚微米尺度的变化。第三,高脂饮食将被用作一个新的平台来研究腔隙-小管重塑如何影响骨折韧性。这些模型利用脂肪对骨细胞健康的不利影响来调节骨陷窝-骨小梁重塑活动。该项目的关键结果是(1)重塑骨细胞的数量和位置,并确定腔隙-小管重塑是否与骨组织应变相关,(2)在接近重塑和非重塑骨细胞的生理相关分辨率下的骨组成和机械性能,以及(3)确定腔隙-小管重塑是否有益地影响骨折韧性。 该项目由生物力学和机械生物学项目以及刺激竞争性研究的既定项目(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知识价值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

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Cheryl Ackert-Bicknell其他文献

38 MOUSE VOIDING PATTERNS ARE STRAIN-SPECIFIC: A NOVEL ASSAY FOR AGE-RELATED DEVELOPMENT OF LOWER URINARY TRACT SYMPTOMS (LUTS)
  • DOI:
    10.1016/j.juro.2013.02.1413
  • 发表时间:
    2013-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Weiqun Yu;Warren Hill;John Larigakis;Cheryl Ackert-Bicknell;David Harrison;Gary Churchill;Mark Zeidel
  • 通讯作者:
    Mark Zeidel
13. Understanding the impact of low-density lipoprotein levels and lipid-lowering agents on rates of pseudarthrosis after anterior cervical discectomy and fusion
  • DOI:
    10.1016/j.spinee.2024.06.457
  • 发表时间:
    2024-09-01
  • 期刊:
  • 影响因子:
  • 作者:
    Ankit Hirpara;Cheryl Ackert-Bicknell;Vikas V. Patel
  • 通讯作者:
    Vikas V. Patel

Cheryl Ackert-Bicknell的其他文献

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