CAREER: Temporal Dynamics of Cartilage Redox Balance

这个由学院早期职业发展计划资助的项目的主要研究目标是在关节软骨中建立响应机械刺激的氧化还原平衡的变化。氧化还原，即氧化剂和抗氧化剂的比例，由于许多疾病而变得不平衡，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是很清楚。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结果。该项目包括机械加载软骨，并使用光学氧化还原成像测量由此产生的氧化还原平衡的变化，该成像最近被证明对关节软骨有效，并能够评估随着时间的推移氧化还原平衡对刺激的响应。这项研究的结果将通过确定氧化还原平衡随时间的变化而推进软骨机械生物学领域，这些变化尚未被探索。在未来，这项研究的结果可以为关节疾病的治疗方法提供参考。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认同感发展，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，即氧化剂(电子受体)和抗氧化剂(电子供体)的比率，在许多疾病中会发生变化。氧化还原平衡也会在短时间内动态变化，以响应机械刺激。健康和疾病关节软骨中氧化还原平衡的短期时间动力学尚未建立。确定这些动力学参数将促进对软骨机械生物学的理解。最近将光学氧化还原成像应用于关节软骨，可以实时、纵向地评估软骨的氧化还原平衡。这项研究将使用光学氧化还原成像来建立软骨的机械生物学(氧化还原)反应。这个项目的具体目标是：(1)建立机械刺激后软骨氧化还原平衡的时间动力学；(2)确定光学氧化还原成像测量的氧化还原平衡与其他指标之间的相关性，包括活性氧物种、线粒体去极化、细胞死亡、细胞衰老和基因表达。这项研究将进一步了解作为软骨区和疾病状态函数的REPSECT软骨对氧化还原平衡的短期机械生物学反应。这一奖项反映了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。

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.