CAREER: Temporal Dynamics of Cartilage Redox Balance

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

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.