Trainee Lightning Talk: Emma Stowe

Exercise and Disuse Initiate Adaptive ECM Remodeling to Shift Tendon Mechanohomeostasis

ABSTRACT

Healthy tendon cells sense changes in their mechanical environment and re-calibrate ECM turnover balance to meet functional needs of the tissue. The objective of this study was to utilize step changes in tensile strain to investigate adaptations of tendon explants to increased (exercise) or decreased (disuse) strain. We hypothesized that exercise would increase matrix synthesis and improve mechanical function while disuse would reduce matrix synthesis and initiate matrix breakdown. Flexor digitorum longus tendon explants were harvested from 4-month male C57BL/6J mice and cultured in an incubator-housed, tensile-loading bioreactor. Explants were loaded at 1% cyclic strain for 7-days. On day 7, the exercise group experienced a step increase to a magnitude of 5% cyclic strain study while disuse group was subjected to stress deprived conditions. Control tissues were loaded at 1% cyclic strain for the entire culture period. ECM remodeling was assessed before and after step changes in tensile strain. We found that tendons are able to sense both increases and decreases in mechanical strain to initiate adaptive remodeling mechanisms. Supporting our hypothesis, we see that exercised tendons become stronger and more elastic. Upregulation of small-leucine-rich proteoglycans (SLRPs) and TGF-β with exercise suggests an adaptation involving support molecules that aid in incorporation and organization of collagen into a functional tissue. While exercise did not result in differences in total protein synthesis or collagen 1 expression, we did see highest collagen content in exercised tendons. Conversely, disuse resulted in decreased expression of SLRPs, TGF-β, and MMP-3, suggesting decreased proteoglycan turnover and compromised remodeling potential. Disuse tendons also show reduced total protein synthesis, reinforcing the idea that mechanical demand drives ECM incorporation. Our current work demonstrates that tendon explants remain mechanically sensitive to dynamic loading even after extended time in culture and that altered mechanical loading triggers adaptations to maintain functional tissue structure.

Emma J. Stowe¹, Yashvi Grover¹, Brianne K. Connizzo¹

¹Boston University, Boston, MA