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Quantification of Bone's Load-Induced Multicellular Intreractions with a Lab-on-a-Chip Platform

使用芯片实验室平台量化骨骼负载引起的多细胞相互作用

基本信息

批准号：
1700299
负责人：
Marnie Saunders
金额：
$ 32.94万
依托单位：
University of Akron
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1700299&HistoricalAwards=false
关键词：
Quantification Bone Load Induced Multicellular

项目摘要

Bone remodeling is an elegant and tightly orchestrated process by which bone forming cells (osteoblasts) and bone removing cells (osteoclasts) work in concert to add or remove bone. In mechanically-induced bone remodeling, bone communication cells (osteocytes) are believed to sense the stimulus and then direct the remodeling response. While this theory is generally accepted, there is still much to understand about how these interactions are coordinated. Current research techniques do not allow for these signals to be fully studied. Understanding bone remodeling at the cellular level is important if the process is to be manipulated to improve bone healing after injury and to minimize the impact of bone diseases, such as osteoporosis. This project is developing a novel lab-on-a-chip system that will incorporate all three types of bone cells and will permit the cell-to-cell signals to be isolated and identified. For the first time, the difference between mechanically generated signals and biochemical signals are being clearly identified. These systems are being studied for both normal stress loading scenarios and overloading stress scenarios, for which the induced an overall response could be bone growth or bone damage, respectively. In addition to incorporating this research into undergraduate and graduate courses, planned outreach activities include the development of a learning community for inner city sixth graders who will participate in a two-year summer camp. The learning community is designed to provide a peer group for the students, with the goal of working with these like-minded students to graduate from high school and to matriculate in college. Current experimental techniques are not appropriate for the separation of mechanically-derived cues for bone remodeling from soluble cues for this phenomenon. For example, in vitro cell models generally isolate one cell type and study its isolated response, while in vivo models require animal sacrifice and represent the remodeling environment at the time of sacrifice. To effectively study the multicellular interactions that occur in remodeling, models are needed that accurately recapitulate the environment. To that end, this research project is developing an in vitro, lab-on-a-chip bone remodeling platform that incorporates osteocytes, osteoclasts and osteoblasts and enables quantification of functional outcomes (i.e., bone formation and resorption). The experimental platform is then being utilized to address the role of soluble signals, cell-cell communication, and cell contact in mechanically-induced remodeling responses in physiological load and overload. Soluble activity is being analyzed by quantifying the effects of loading-induced osteocyte conditioned medium on bone formation and resorption. Experiments are then being repeated in co-cultures of osteoclasts and osteoblasts to incorporate soluble signals and cell contact allowing the contribution of the mechanisms to be determined. Finally, experiments are being repeated in gap-junction deficient systems to allow the contribution of cell communication to be determined.

骨重建是一个优雅的和紧密协调的过程，其中骨形成细胞（成骨细胞）和骨去除细胞（破骨细胞）协同工作，以增加或去除骨。在机械诱导的骨重建中，骨通讯细胞（骨细胞）被认为是感知刺激，然后指导重建反应。虽然这一理论被普遍接受，但关于这些相互作用是如何协调的，仍然有很多东西需要了解。目前的研究技术不允许对这些信号进行充分研究。了解细胞水平上的骨重建是很重要的，如果这个过程是被操纵，以改善损伤后的骨愈合，并尽量减少骨疾病的影响，如骨质疏松症。该项目正在开发一种新型的芯片实验室系统，该系统将整合所有三种类型的骨细胞，并允许分离和识别细胞间的信号。这是第一次，机械产生的信号和生化信号之间的差异被清楚地确定。这些系统正在研究正常应力加载情况和过载应力情况，其中诱导的整体反应可能是骨生长或骨损伤，分别。除了将这项研究纳入本科和研究生课程，计划的推广活动包括为将参加为期两年的夏令营的内城六年级学生开发一个学习社区。学习社区的目的是为学生提供一个同龄人小组，与这些志同道合的学生一起工作，从高中毕业，并在大学录取的目标。目前的实验技术是不适合的机械衍生线索骨重建从可溶性线索这种现象的分离。例如，体外细胞模型通常分离一种细胞类型并研究其分离的反应，而体内模型需要动物处死并代表处死时的重塑环境。为了有效地研究重塑中发生的多细胞相互作用，需要准确概括环境的模型。为此，该研究项目正在开发一种体外实验室芯片骨重塑平台，该平台整合了骨细胞、破骨细胞和成骨细胞，并能够量化功能结果（即，骨形成和再吸收）。然后，该实验平台被用于解决可溶性信号，细胞间通讯和细胞接触在生理负荷和过载中机械诱导的重塑反应中的作用。通过定量负荷诱导的骨细胞条件培养基对骨形成和吸收的影响来分析可溶性活性。然后在破骨细胞和成骨细胞的共培养物中重复实验，以掺入可溶性信号和细胞接触，从而确定机制的贡献。最后，在间隙连接缺陷系统中重复实验，以确定细胞通讯的贡献。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Current Trends in Osteoporosis Diagnostics: An Opportunity for Quantitative Ultrasound and Biomarkers

骨质疏松症诊断的当前趋势：定量超声和生物标志物的机会

DOI：
10.26717/bjstr.2019.23.003838
发表时间：
2019
期刊：
Biomedical Journal of Scientific & Technical Research
影响因子：
0
作者：
Saunders, Marnie M
通讯作者：
Saunders, Marnie M

Lab-on-a-chip platforms for quantification of multicellular interactions in bone remodeling

DOI：
10.1016/j.yexcr.2018.02.027
发表时间：
2018-04-01
期刊：
EXPERIMENTAL CELL RESEARCH
影响因子：
3.7
作者：
George, Estee L.;Truesdell, Sharon L.;Saunders, Marnie M.
通讯作者：
Saunders, Marnie M.

A Lab-On-A-Chip Platform for Stimulating Osteocyte Mechanotransduction and Analyzing Functional Outcomes of Bone Remodeling

用于刺激骨细胞力转导和分析骨重塑功能结果的芯片实验室平台

DOI：
10.3791/61076
发表时间：
2020
期刊：
Journal of Visualized Experiments
影响因子：
0
作者：
Truesdell, Sharon L.;George, Estee L.;Van Vranken, Christopher C.;Saunders, Marnie M.
通讯作者：
Saunders, Marnie M.

3D Printed Loading Device for Inducing Cellular Mechanotransduction via Matrix Deformation

通过基质变形诱导细胞机械传导的 3D 打印加载装置