Mechanical loading modulates heterotopic ossification in calcific tendinopathy through the mTORC1 signaling pathway.

Excessive mechanical loading is a major factor affecting heterotopic ossification (HO), which is a major pathological alteration in calcific tendinopathy. However, physical therapies with mechanical loading as the functional element have exhibited promising results in the treatment of calcific tendinopathy. The dual effects that mechanical loading may have on the pathogenesis and rehabilitation of calcified tendinopathy remain unclear. The present study was designed to investigate the effects of mechanical loading on HO in calcific tendinopathy. In the present study, a tendon cell in vitro stretch model and an Achilles tenotomy rat model were used to simulate different elongation mechanical loading scenarios in order to investigate the effects of mechanical loading on HO of the tendon. In addition, rapamycin, a selective mammalian target of rapamycin complex-1 (mTORC1) signaling pathway inhibitor, was employed to determine whether mechanical loading modulates heterotopic ossification in calcific tendinopathy through the mTORC1 signaling pathway. The data indicate that mechanical loading modulated HO of the tendon through the mTORC1 signaling pathway, and that low elongation mechanical loading attenuated HO, while high elongation mechanical loading accelerated HO in vivo. This study may improve the understanding of the effect of physical therapies used to treat calcific tendinopathy, so as to guide clinical treatment more effectively. Furthermore, rapamycin may be a potential drug for the treatment of calcific tendinopathy.