Loss of STAT1 in Bone Marrow-Derived Cells Accelerates Skeletal Muscle Regeneration

BACKGROUND: Skeletal muscle regeneration is a complex process which is not yet completely understood. Evidence suggested that the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway may have a role in myogenesis. In this study, we aim to explore the possible role of STAT1 in muscle regeneration. METHODS: Wild-type and STAT1 knockout mice were used in this study. Tibialis anterior muscle injury was conducted by cardiotoxin (CTX) injection. Bone marrow transplantation and glucocorticoid treatment were performed to manipulate the immune system of the mice. RESULTS: Muscle regeneration was accelerated in STAT1−/− mice after CTX injury. Bone marrow transplantation experiments showed that the regeneration process relied on the type of donor mice rather than on recipient mice. Levels of pro-inflammatory cytokines, TNFα and IL-1β, were significantly higher in STAT1−/− mice at 1 day and/or 2 days post-injury, while levels of anti-inflammatory cytokine, IL-10, were lower in STAT1−/− mice at 2 days and 3 days post-injury. Levels of IGF-1 were significantly higher in the STAT1−/− mice at 1 day and 2 days post-injury. Furthermore, the muscle regeneration process was inhibited in glucocorticoid-treated mice. CONCLUSIONS: Loss of STAT1 in bone marrow–derived cells accelerates skeletal muscle regeneration.