| The major finding from this study was that beta2 integrins, cell surface receptors that mediate functions of neutrophils and macrophages (inflammatory cells) contribute to overload-induced muscle hypertrophy. Plantaris muscles of wild type and beta2 integrin deficient (CD18-/-) mice were subjected to 3, 7, or 14 days of muscle overload via bilateral synergist ablation. Following 7 days of muscle overload, wild type mice showed enhanced myofiber regeneration (central nucleation) and larger regenerating myofibers when compared to CD18-/- mice. Furthermore, gene expression of muscle regulatory factors MyoD and myogenin were significantly elevated in wild type compared to CD18-/- mice across all time point of overload. Additionally, beta 2 integrin expression contributed to enhanced phosphorylation of p70 at 7 days of overload compared to CD18-/- mice, indicating that beta 2 integrins may contribute to signaling for protein synthesis. Notably, there was a temporal relationship between the accumulation of inflammatory cells and myofiber regeneration and signaling for protein synthesis in wild type but not CD18-/- mice following overload. These events preceded increases in muscle wet and dry mass, total protein content, and increased myofiber cross sectional area (CSA) for wild type but not CD18-/- mice at 14 days of overload. Lastly, muscle extracts from 7 day overloaded wild type and CD18-/- plantaris were tested for their ability to influence the fusion and/or hypertrophy of cultured C2C12 muscle cells. Although, extract from CD18-/- mice increased myosin heavy chain protein expression by muscle cells, myogenin protein expression and the fusion index were not influenced by extract treatment. Furthermore, myotube size (maximum width), a measure of myotube hypertrophy, was not influenced by extract treatment. In conclusion, beta 2 integrin signaling in inflammatory cells contributes to the cellular and molecular events required for overload-induced muscle hypertrophy. However, the underlying mechanism/s for this contribution remains to be determined. |
