Novel muscle contusion injury model and repair mechanism
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This study investigates the skeletal muscle repair and regeneration process following blunt trauma injury in murine models. Skeletal muscle injury is recorded most often in sports injuries and include strains and sprains, contusions, and bruising, however, there is growing consensus about the role skeletal muscle plays in the reparative process of bone fractures. Skeletal muscle stem cells or satellite cells are mesenchymal stem cell derived cells that exist between the basal lamina and cell membrane of muscle fibers usually in close proximity to capillary beds. After a traumatic injury, satellite cells respond to the influx of signaling from immune cells, oxygen tension, and myogenic proteins which influence differentiation into myoblasts for repair of tissue damage. Research continues to elucidate the relationship between bone and skeletal muscle following trauma injuries. Skeletal muscle stem cells play a vital role in fracture healing, and in certain conditions, are even induced into the osteogenic pathway. The goals of this study are to characterize the temporal progression of myogenesis during muscle repair that will be used with future studies of muscle and bone injury. And to identify potential crosstalk mechanisms between muscle and bone repair during trauma. In our experiment model trauma was introduced to mice with a modified muscle contusion device where a weight was dropped onto the femoral quadriceps muscles and the quadriceps and biceps muscle tissues were harvested at post-operative days (POD) 2, 4, 12, 16, and 24. Reverse-Transcriptase Quantitative Polymerase Chain Reaction was used to analyze gene expression profiles for satellite/stem cells (Pax7 and Prx1), muscle regeneration (MyoD, Myf5, Myl2, and Myh1), angiogenesis (VegfA, VegfR2), myokine (Myostatin and IL6), and BMP signaling (ID1). Our findings indicate that both Pax7 and Prx1 expression slightly decreased after injury but showed a significant (p<0.05) increase and peak of expression at POD 16 in the femoral quadriceps muscles. The early myogenic genes, MyoD and Myf5 peaked early at POD 4 while the adult myofiber markers, Myl2 and Myh2, peaked later at POD 16 in the femoral quadriceps muscles. Only slight changes were observed in the femoral biceps muscles. The angiogenic genes peaked at POD16 in the femoral quadriceps muscles and POD 12 in the femoral biceps muscles. The expression of Myostatin, an inhibitor of muscle mass, decreased early (POD 4 and 12) however showed a non-significant increase at POD 16 in the femoral quadriceps muscles. Lastly, the expression of ID1, which is downstream target of BMP signaling peaked early at POD 4 in the femoral quadriceps muscles. These data indicates that stem/satellite cells decrease in response to muscle injury but by POD 4, myogenic commitment and programming occurs. While early myogensis occurs, BMP signaling peaks and Myostatin expression decreases suggesting a coordinated event. Adult myofiber regeneration occurs in parallel to angiogenesis. The myogenic events were primarily isolated to the injured femoral quadriceps muscles. This model of muscle injury can be used to study muscle regeneration within context to bone injury.