Relaxin Regulates MMP Expression and Promotes Satellite Cell Mobilization During Muscle Healing in Both Young and Aged Mice

Abstract

The polypeptide hormone relaxin has been proven to be effective in promoting both the remodeling and regeneration of various tissues, including cardiac muscle. In addition, our previous study demonstrated that relaxin is beneficial to skeletal muscle healing by both promoting muscle regeneration and preventing fibrosis formation. However, the molecular and cellular mechanisms of relaxin in regulating both myogenic cell differentiation and muscle healing process are still unclear. In this study, C2C12 mouse myoblasts and primary human myoblasts were treated with relaxin to investigate its potential effect in vitro; relaxin was also injected intramuscularly into the injured site of the mouse on the second day after injury to observe its function in vivo, especially in the aged muscle. Results showed that relaxin promoted myogenic differentiation, migration, and activation of matrix metalloproteinases (MMPs) of cultured myoblasts in vitro. In the injured muscle, relaxin administration promoted the activation of Pax7-positive skeletal muscle satellite cells and increased its local population compared with nontreated control muscles. Meanwhile, both angiogenesis and revascularization were increased, while the extended inflammatory reaction was repressed in the relaxin-treated injured muscle. Moreover, relaxin similarly promoted muscle healing in mice with aged muscle. These results revealed the multiple effects of relaxin in systematically improving muscle healing as well as its potential for clinical applications in patients with skeletal muscle injuries and diseases. (Am J Pathol

MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx/SCID mice

“…47 We detected in this study that MDSCs themself also contain certain level of MMP1, which expresses as similar as in the MMP1 genetic engineered MDSCs (Fig 1C). We also found that MMP1 gene transfer has no significant effect in natural MDCS' characteristics, including the study of muscle engraftment after intramuscular injection into mdx mice, indicating that MMP potentially effects stem cell behaviors in a dose dependent manner.…”

Relaxin counteracts the altered gastric motility of dystrophic (mdx) mice: functional and immunohistochemical evidence for the involvement of nitric oxide

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The Effect of Physiological Stimuli on Sarcopenia; Impact of Notch and Wnt Signaling on Impaired Aged Skeletal Muscle Repair

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