Eccentric contraction-dominant exercise leads to molecular biological changes in enthesis and enthesopathy-like morphological changes.

Entheses, which are tendon-to-bone attachment sites in the musculoskeletal system, play important roles in optimizing the mechanical stress and force transmitted from the muscle to the bone. Sports-related enthesopathy shows pathological features, including hyperplasia of the fibrocartilage (FC) region in the enthesis. The amount of exercise and type of muscle contraction during movement is involved in the pathogenesis of sports-related enthesopathy; however, the details of this condition are unclear. Here we examined the molecular pathways involved in the morphological changes of the muscle-tendon-enthesis complex and enthesis FC region in the supraspinatus muscle enthesis of mice under different exercise conditions. Following intervention, morphological changes in the muscle-tendon-enthesis complex were initiated in the eccentric contraction-dominant exercise group at 2 weeks, with activation of the transforming growth factor-ß (TGFß) superfamily pathway predicted by proteome and ingenuity pathway analyses. Histological and molecular biological analyses confirmed the activation of the TGFß/bone morphogenetic protein (BMP)-Smad pathway. The concentric contraction-dominant exercise group showed no change in the morphology of the muscle-tendon-enthesis complex or activation of the TGFß/BMP-Smad pathway, despite overuse exercise. Statement of Clinical Significance: These results suggest that eccentric contraction-dominant exercise induces sports-related enthesopathy-like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor-ß superfamily pathway in enthesis. Statement of Clinical Significance: These results suggest that eccentric contraction-dominant exercise induces sports-related enthesopathy-like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor-ß superfamily pathway in enthesis.

Structural and pathological changes in the enthesis are influenced by the muscle contraction type during exercise.

Mechanical stress is involved in the onset of sports-related enthesopathy. Although the amount of exercise undertaken is a recognized problem during disease onset, changes in muscle contraction type are also involved in the increase in mechanical stress during exercise. This study aimed to clarify the effects of increased mechanical stress associated with muscle contraction type and amount of exercise on enthesis. Twenty mice underwent treadmill exercise, and the muscle contraction type and overall load during exercise were adjusted by varying the angle and speed conditions. Histological analysis was used to the cross-sectional area of the muscle; area of the enthesis fibrocartilage (FC), and expression of inflammation-, degeneration-, and calcification-related factors in the FC area. In addition, the volume and structure of the bone and FC area were examined using microcomputer imaging. Molecular biological analysis was conducted to compare relative expression levels of inflammation and cytokine-related factors in tendons. The Overuse group, which increased the amount of exercise, showed no significant differences in parameters compared to the sedentary mice (Control group). The mice subjected to slow-speed downhill running (Misuse group) showed pathological changes compared to the Control and Overuse groups, despite the small amount of exercise. Thus, the enthesis FC area may be altered by local mechanical stress that would be increased by eccentric muscle contraction rather than by mechanical stress that increases with the overall amount of exercise. Clinical Significance: The muscle contraction type might be more involved in the onset of sports-related enthesopathy rather than the amount of exercise.