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To stimulate healing and prevent tendinosis through optimized physical exercise, it is important to elucidate the tendon response to repetitive mechanical loading. However, the study of this response is challenging due to complex cell-matrix interactions. In an initial approximation, the authors examined tendon mechanical response only, and did not consider cellular activity. The authors investigated the hypothesis that mechanical degradation occurs relatively rapidly (<24 h) even at very low stress levels. The authors subjected rat tail tendons to mechanical loadings oscillating between 0 and 1.5 MPa up to one of three fatigue levels: 4% strain, 8% strain, or rupture. Using non-destructive mechanical tests, changes in tendon strain and compliance over the entire fatigue testing period were evaluated. Using microscopy techniques, the structural evidence of mechanical degradation was examined. The changes in tendon strain and compliance progressed nonlinearly and accelerated before rupture which took place around the 15-h mark. Histological analyses revealed a higher degree of alteration in the collagen network at increased fatigue levels. At rupture, local zones of damage with low fibril density were evident. These results imply that a repair process must act rapidly at critical sites; otherwise, enzymatic degradation could cause further damage in the manner of a vicious cycle. [ABSTRACT FROM AUTHOR]