RESUMO
In the present study, we investigated the possible involvement of the TGF-ß/Smad signaling pathway in the osteopontin-derived SVVYGLR (SV) peptide-mediated migratory activities of myogenic cells and evaluated the facilitative effects of the SV peptide on the differentiation of myogenic cells in vitro. The SV peptide-induced migration in both human-derived satellite cells and myoblasts was substantially suppressed by the TGF-ß1 receptor inhibitor SB431542 or SB505124. Besides, the expression level of the Smad3 phosphorylation was further enhanced by the addition of the SV peptide in comparison with control groups. Furthermore, an increase in the expression of myogenin-positive nuclei and a higher number of nascent myotubes with myosin heavy chain expression was confirmed in cultured myoblasts supplemented with the SV peptide. These results suggest that the involvement of the TGF-ß/Smad signaling pathway in the SV peptide-mediated migration and the facilitative effect of the SV peptide on the differentiation of myogenic cells into myotubes.
Assuntos
Transdução de Sinais , Fator de Crescimento Transformador beta1 , Diferenciação Celular , Movimento Celular , Humanos , OligopeptídeosRESUMO
The present study was designed to evaluate the effects of the osteopontin-derived multifunctional short peptide, SVVYGLR (SV) peptide on the biological properties of skeletal muscle-specific myogenic cells. We employed human-derived satellite cells (HSkMSC) and skeletal muscle myoblasts (HSMM) and performed a series of biochemical experiments. The synthetic SV peptide showed no influence on the proliferation and adhesion properties of HSkMSC and HSMM, while it showed a significant increase in cell motility, including migration activities upon treatment with the SV peptide. In a rat model with volumetric loss of masticatory muscle, immunohistochemical staining of regenerating muscle tissue immediately after injury demonstrated an increase of the number of both MyoD- and myogenin-positive cells in SV peptide-treated group. These results suggest that SV peptide plays a potent role in facilitating skeletal muscle regeneration by promoting the migration, and differentiation of myogenic precursor and progenitor cells.
Assuntos
Músculo Esquelético , Regeneração , Animais , Diferenciação Celular , Movimento Celular , Oligopeptídeos , RatosRESUMO
Oral and maxillofacial skeletal muscles are critical for oral motor functions, and severe damage to these muscles by trauma or surgery may lead to persistent functional impairment. This study investigated the effects of SVVYGLR (SV) peptide, a thrombin-cleaved osteopontin-derived motif, on histopathological wound healing and functional repair after severe injury of skeletal muscles. A rat model of volumetric muscle loss bilateral masseter muscle was developed. A single dose of SV-peptide or phosphate-buffered saline (PBS) was separately injected into the injured muscle belly. Histopathological and functional analyses were performed 1-8 weeks after the treatment. Behavioral analysis during free-feeding revealed that the feeding rate markedly increased in the SV-peptide group, in contrast, the PBS group showed fewer changes after the injury. Electromyogram recordings from injured muscles demonstrated amplification of rectified burst activity over time accompanied by increased maximal amplitude and duration in the SV-peptide group, in contrast, the PBS group showed moderate changes. A lissajous figure for bilateral masseter muscle activities also revealed superior functional recovery by the SV-peptide treatment. The SV-peptide also facilitated regeneration of muscles composed of matured myofibers with a greater diameter compared to the PBS group. In addition, granulation in the earlier period and fibrosis in the later period of wound healing were significantly inhibited by the SV-peptide treatment but not by the PBS treatment. Therefore, local application of the SV-peptide could help facilitate regeneration of muscles, inhibition of fibrosis, and improvement of functional impairment of oral and maxillofacial skeletal muscles damaged by severe trauma or surgery.