Inhibition of myostatin signal pathway may be involved in low-intensity pulsed ultrasound promoting bone healing.

Abstract

Low-intensity pulsed ultrasound (LIPUS) is effective in promoting bone healing, and a myostatin deficiency also has a positive effect on bone formation. In this study, we evaluated the effects of LIPUS on bone healing in rats in vivo and investigated the mechanisms in vitro, aiming to explore whether LIPUS promotes bone healing through inhibition of the myostatin signaling pathway. Rats with both drill-hole defects and MC3T3-E1 cells were randomly assigned to a LIPUS group and a control group. The LIPUS group received LIPUS treatment (1.5MHz, 30mW/cm2) for 20min/day. After 21days, the myostatin expression in quadriceps was significantly inhibited in the LIPUS group, and remodeling of the newly formed bone in the drill-hole site was significantly better in the LIPUS group than that in the control group, which was confirmed by micro-CT analysis. After 3days, LIPUS significantly promoted osteoblast proliferation; inhibited the expression of AcvrIIB (the myostatin receptor), Smad3, p-Smad3, and GSK-3β; and increased Wnt1 and β-catenin expression. Moreover, translocation of β-catenin from the cytolemma to the nucleus was observed in the LIPUS group. However, these effects were blocked by treatment with myostatin recombinant protein. The results indicate that LIPUS may promote bone healing through inhibition of the myostatin signal pathway.