CAREER: Temporal Dynamics of Cartilage Redox Balance

职业：软骨氧化还原平衡的时间动态

• 批准号: 2237707
• 负责人: Corinne Henak
• 金额: $ 60万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2237707&HistoricalAwards=false
• 关键词: CAREER; Temporal; Dynamics; Cartilage; Redox

The primary research goal of this Faculty Early Career Development (CAREER) program funded project is to establish changes in redox balance in response to mechanical stimuli in articular cartilage. Redox, the ratio of oxidants to antioxidants, becomes imbalanced from many diseases, including osteoarthritis. Redox balance also changes in response to stimuli such as mechanical loading. However, the temporal response of redox balance after mechanical loading in articular cartilage is not well understood. Determining this response would advance the understanding of cartilage behavior, which can be used in the future to advance health outcomes in patients with joint disease. This project involves mechanically loading cartilage and measuring the resulting change in redox balance using optical redox imaging, which was recently shown to be valid for articular cartilage and enables the evaluation of redox balance over time in response to stimuli. The outcomes of this research will advance the field of cartilage mechanobiology, by identifying changes in redox balance over timescales that have not been explored. In the future, the outcomes of this study can inform therapeutic approaches for joint disease. This project will include K12 outreach, introducing K12 students to mechanobiology and redox balance through interactive demonstrations. Researchers will also involve undergraduate students in the research activities and develop methods to improve students’ development of engineering identity, thereby supporting science and engineering education.This research project will identify the effect of mechanical loading on redox balance in articular cartilage. Redox balance, the ratio of oxidants (electron acceptors) to antioxidants (electron donors), shifts for many diseases. Redox balance also changes dynamically over short timeframes in response to mechanical stimuli. The short-term temporal dynamics of redox balance in healthy and diseased articular cartilage have not been established. Determining these dynamics will advance the understanding of cartilage mechanobiology. Recent application of optical redox imaging to articular cartilage enables real-time, longitudinal evaluation of cartilage redox balance.. This research will use optical redox imaging to establish cartilage mechanobiological (redox) response. The specific goals of this project are to (1) establish the temporal dynamics of cartilage redox balance following mechanical stimuli; and (2) determine correlations between redox balance as measured by optical redox imaging and other metrics including reactive oxygen species, mitochondrial depolarization, cell death, cell senescence, and gene expression.This research will further understanding of the short-term mechanobiological response of cartilage with repsect to redox balance, as a function of cartilage zone and disease state.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.

该学院早期职业发展（CAREER）计划资助项目的主要研究目标是建立关节软骨中响应机械刺激的氧化还原平衡变化。氧化还原，氧化剂与抗氧化剂的比例，在许多疾病中变得不平衡，包括骨关节炎。氧化还原平衡也会因机械负荷等刺激而改变。然而，关节软骨机械负荷后氧化还原平衡的时间响应还不清楚。确定这种反应将促进对软骨行为的理解，这可以在未来用于改善关节疾病患者的健康状况。该项目涉及机械加载软骨并使用光学氧化还原成像测量由此产生的氧化还原平衡变化，该成像最近被证明对关节软骨有效，并能够评估氧化还原平衡随时间的变化对刺激的反应。这项研究的结果将通过确定尚未探索的时间尺度上氧化还原平衡的变化来推进软骨机械生物学领域。在未来，这项研究的结果可以为关节疾病的治疗方法提供信息。该项目将包括K12外展，通过互动演示向K12学生介绍机械生物学和氧化还原平衡。研究人员还将让本科生参与研究活动，并开发方法来提高学生的工程身份发展，从而支持科学和工程教育。本研究项目将确定机械负荷对关节软骨氧化还原平衡的影响。氧化还原平衡，氧化剂（电子受体）与抗氧化剂（电子供体）的比例，在许多疾病中发生变化。氧化还原平衡也会在短时间内动态变化，以响应机械刺激。健康和患病关节软骨中氧化还原平衡的短期时间动态尚未建立。确定这些动力学将促进对软骨机械生物学的理解。最近应用光学氧化还原成像到关节软骨，使实时，纵向评估软骨氧化还原平衡。这项研究将使用光学氧化还原成像来建立软骨机械生物学（氧化还原）反应。本课题的具体目标是：（1）建立机械刺激后软骨氧化还原平衡的时间动力学;以及（2）确定通过光学氧化还原成像测量的氧化还原平衡与其它度量之间的相关性，所述其它度量包括活性氧物质、线粒体去极化、细胞死亡、细胞衰老，这项研究将进一步了解软骨对氧化还原平衡的短期机械生物学反应，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。