Understanding Regulators of Collagen Crosslinking Enzymes for Tendon Formation

Regents Of The University Of Idaho, Moscow ID

Investigators

Abstract

Tendons act as a mechanical connection from muscle to bone. Understanding how tendons develop mechanical function is important because tendon injuries are common, treatment options are limited, and damaged tendons rarely regain their full strength. Collagen is a major contributor to tendon strength. However, much is unknown about the conditions that influence collagen formation during normal tendon development. For example, several types of enzymes crosslink and stabilize collagen in tendons, but how cells coordinate the production of these collagen crosslinking enzymes during tendon development is unknown. This project addresses this knowledge gap by exploring the signals that control enzyme production by cells. This research will generate new knowledge on how collagen crosslinking is regulated. Findings from this research will contribute to a greater understanding of the mechanisms of tendon formation and may lead to advanced therapies to treat the altered mechanical function and disability found with tendon injuries. Integral to the project are activities to improve retention in STEM and the diversity of graduates in engineering. The project creates hands-on research experiences and the writing exercises for students enrolled in a multidisciplinary engineering course. It also funds undergraduates to conduct faculty-mentored research, develop and submit NSF graduate research fellowship applications, and present their research at scientific conferences. Finally, the project includes K-12 outreach activities and laboratory tours. The scientific goal of this research is to define the mechanisms that control collagen crosslinking enzyme production by cells. Adult stem cells and tendon cells isolated from developing rat tendons associated with high forces, the Achilles tendon, and low forces, the tail tendon, will be evaluated in culture as model systems to determine if these cell populations have unique control mechanisms. To test mechanically responsive pathways that regulate collagen crosslinking enzyme production, cells will be exposed to a range of mechanical stimuli using a bioreactor and treated with targeted cell signaling pathway inhibitors. The role of biological signaling in enzyme production will be evaluated using different biochemical growth factors that are known to impact tendon growth and injury, while conducting cell signaling pathway inhibition and analysis. Research outcomes will advance knowledge of the mechanisms that regulate collagen crosslinking enzyme production by tendon and stem cells. This project is jointly funded by Biomechanics & Mechanobiology (BMMB) Program and the Established Program to Stimulate Competitive Research (EPSCoR). 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.