Treadmill exercise facilitated rotator cuff healing is coupled with regulating periphery neuropeptides expression in a murine model.

Postoperative exercise has been found able to accelerate bone-tendon (B-T) healing. In this study, we systematically compared tendon-to-bone healing in mice subjected to postoperative treadmill exercise and free cage recovery in a murine rotator cuff repair model. Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon (SST) detachment and repair were randomly allocated into treadmill group and control group. Treadmill group received daily treadmill running initiated from postoperative day 7 while the control group was allowed free cage activity. Mice were euthanized at postoperative 4 and 8 weeks for synchrotron radiation micro-computed tomography (SR-μCT), histology and biomechanical tests to investigate the effect of treadmill running on B-T healing. The results indicated that treadmill running initiated at day 7 postoperatively was able to accelerate B-T healing, as evidenced by better tendon-to-bone maturation and increased mechanical property. Recent studies show that peripheral neuropeptides are closely associated with musculoskeletal tissue repair. We furtherly conducted quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining to investigate the temporal-spatial expression of calcitonin gene-related peptide (CGRP), substance P (SP), and peripheral neuropeptide Y (NPY) to verify whether they are related to rotator cuff healing. Our results show increased expression of CGRP, SP, and NPY at the healing site under the effect of mechanical stimulation. In conclusion, delayed postoperative exercise with moderate strength appears to accelerate the early phase of B-T healing, a process that may prove to be linked to increased expression of periphery neuropeptides known to play a role in tissue healing.