Molecular response of the patellar tendon to fatigue loading explained in the context of the initial induced damage and number of fatigue loading cycles.

Accumulation of sub-rupture fatigue damage has been implicated in the development of tendinopathy. We previously developed an in vivo model of damage accumulation using the rat patellar tendon. Our model allows us to control the input loading parameters to induce fatigue damage in the tendon. Despite this precise control, the resulting induced damage could vary among animals because of differences in size or strength among their patellar tendons. In this study, we used number of applied cycles and initial (day-0) parameters that are indicative of induced damage to assess the molecular response 7 days after fatigue loading. We hypothesized that day-0 hysteresis, elongation, and stiffness of the loading and unloading load-displacement curves would be predictive of the 7-day molecular response. Results showed correlations between the 7-day molecular response and both day-0 elongation and unloading stiffness. Additionally, loading resulted in upregulation of several extracellular matrix genes that suggest adaptation; however, several of these genes (Col-I, -XII, MMP 2, and TIMP 3) shut down after a high level of damage was induced. We showed that evaluating the 7-day molecular profile in light of day-0 elongation provides important insight that is lost from comparing number of fatigue loading cycles only. Our data showed that loading generally results in an adaptive response. However, the tendon's ability to effectively respond deteriorates as greater damage is induced.