CAREER: Temporal Dynamics of Cartilage Redox Balance

这项由教师早期职业发展（Career）计划资助的项目的主要研究目标是建立关节软骨在机械刺激下氧化还原平衡的变化。氧化还原，即氧化剂与抗氧化剂的比例，在包括骨关节炎在内的许多疾病中变得不平衡。氧化还原平衡也会随着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反应尚不清楚。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结果。该项目涉及对软骨进行机械加载，并使用光学氧化还原成像测量氧化还原平衡的变化，该成像最近被证明对关节软骨有效，并且可以评估对刺激的氧化还原平衡随时间的变化。这项研究的结果将通过确定氧化还原平衡在时间尺度上的变化而推动软骨力学生物学领域的发展。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，并制定方法来提高学生的工程身份发展，从而支持理工科教育。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）与抗氧化剂（电子供体）的比例，在许多疾病中发生变化。氧化还原平衡也在短时间内动态变化，以响应机械刺激。健康和病变关节软骨中氧化还原平衡的短期动态尚未确定。确定这些动力学将促进对软骨力学生物学的理解。最近光学氧化还原成像在关节软骨上的应用使软骨氧化还原平衡的实时、纵向评估成为可能。本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。该项目的具体目标是：(1)建立机械刺激后软骨氧化还原平衡的时间动态；(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（包括活性氧、线粒体去极化、细胞死亡、细胞衰老和基因表达）之间的相关性。本研究将进一步了解软骨在氧化还原平衡方面的短期力学生物学反应，作为软骨带和疾病状态的功能。该奖项反映了美国国家科学基金会的法定使命，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。

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.