Abstract
The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO) mice and wild type (WT) mice. The mice were sacrificed at 3, 14, and 28 days post-operation. The results of hematoxylin-eosin staining and immunofluorescence of muscle membrane indicated that muscle regeneration was delayed in p21 KO mice. Cyclin D1 mRNA expression and both Ki-67 and PCNA immunohistochemistry suggested that p21 deficiency increased cell cycle and muscle cell proliferation. F4/80 immunohistochemistry also suggested the increase of immune response in p21 KO mice. On the other hand, both the mRNA expression and western blot analysis of MyoD, myogenin, and Pax7 indicated that muscular differentiation was delayed in p21KO mice. Considering these results, we confirmed that muscle injury causes an increase in cell proliferation. However, muscle differentiation in p21 KO mice was inhibited due to the low expression of muscular synthesis genes, leading to a delay in the muscular regeneration. Thus, we conclude that p21 plays an important role in the in vivo healing process in muscular injury.
Highlights
Sports-related muscle injuries are among the most common soft tissue injuries [1,2]
The injured muscle was almost recovered 28 days after injury in p21 KO group. These results indicated that muscle regeneration was delayed in p21 KO mice
The histological findings and experiments conducted to determine weight of the injured muscle demonstrated that the injured muscle showed almost full recovery at 14 days in wild type (WT) mice, which was consistent with another muscle injury model [29]
Summary
Sports-related muscle injuries are among the most common soft tissue injuries [1,2] In most cases, they are caused by sudden overstretching of the contracted muscle, leading to muscle fiber damage [3,4]. They are caused by sudden overstretching of the contracted muscle, leading to muscle fiber damage [3,4] Such injuries do not usually necessitate surgery, a majority of these can be treated with conservative therapy [5]. In cases where muscle injury is judged as not being a severe pathological condition, the therapy duration might even be reduced. This reduction in treatment period may lead to recurrence and intensification of damage. The degree of muscular damage considerably affects the individual’s return to sports, mainly in injuries affecting the lower
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