The Role of Inflammation in Skeletal Muscle Healing

Skeletal muscle injury is a common type of injury in sports medicine. After the injury, the traumatized muscle undergoes sequential and overlapped phases of healing, including degeneration, inflammation, regeneration, and fibrosis. Inflammation is an important phase in the natural healing process of many injured tissues. During this phase, various cytokines and cells participate and form a complex environment. Since uncomfortable symptoms are associated with inflammation, current treatments for skeletal muscle injury focus on inhibiting the inflammation phase by using non-steroidal anti-inflammation drugs (NSAIDs). Given that inflammation is shown to be beneficial to the healing process of many other tissues, it is necessary to study its role in skeletal muscle healing in order to improve the healthcare of sports-related injuries. Here, we investigated the role of the inflammation phase in skeletal muscle injury. We initially compared the healing of injured skeletal muscle and the growth of muscle cells with and without the treatment of NS-398, a cyclooxygenase-2 (COX-2) specific NSAID. We observed that NS-398 impaired muscle healing by delaying muscle regeneration and increasing scar tissue formation. NS-398 inhibited the proliferation and differentiation of muscle cells, and the expression of prostaglandin E2 (PGE2) and prostaglandin F2¦Á (PGF2¦Á). Next, we investigated the important components in the inflammation phase, including the COX-Prostaglandins pathway, transforming growth factor-¦Â1 (TGF-¦Â1), and macrophages. We found that PGF2¦Á and PGE2 may promote muscle cell maturation. The expression of TGF-¦Â1, a fibrotic growth factor, may be suppressed by PGE2 but increased by NS-398. Macrophages may promote muscle healing by increasing the release of various cytokines and growth factors, including TGF-¦Â1 and PGE2. These results suggest that various cytokine, growth factor, and cellular components participate in the inflammation phase and cooperate with each other to modulate the healing process. Simply using NSAIDs to block inflammation may not be the optimal treatment in the effort of achieving complete recovery after muscle injury. In conclusion, our results suggest that the inflammation phase is important in skeletal muscle healing and further research to investigate the role of its components is necessary