Background/Aims: The complicated differentiation processes of cells in skeletal muscle against inflammation that induce muscle atrophy are not fully elucidated. Given that skeletal muscle is a secretory organ, we evaluated the effects of inflammation on myogenic signals and myokine expression, and the roles of inflammatory exosomes released by myotubes in myogenic differentiation. Methods: Inflammation was induced by treatment of fully differentiated C2C12 myotubes with a cytokine mixture of TNF-α and INF-γ. Exosome-like vesicles (ELVs) were isolated from conditioned media of control or inflamed myotubes and incubated with myoblasts. The expression of molecular switches that contribute to myogenic differentiation, including several kinases, their downstream targets, and myokines, were evaluated using immunoblot analysis in inflamed myotubes and in myoblasts treated with ELVs. Results: Inflammation activated molecular mechanisms contributing to muscle atrophy, including AMPK, p-38 MAPK and JNK, while inhibiting Akt-mediated myogenic signals. In addition, inflammation induced myostatin expression with suppression of a myostatin-counteracting myokine, decorin. Well-characterized ELVs released from inflamed myotubes induced myoblast inflammation and inhibited myogenic mechanisms while stimulating atrophic signals. Conclusion: Inflammation of skeletal muscle induces muscle atrophy via multiple mechanisms, including the regulation of myokines and kinases. Inflammatory ELVs are likely to contribute to inflammation-induced muscle atrophy.
We describe a rare case of sclerosing osteomyelitis of Garré in a 63-year-old woman with uncontrolled right thigh pain. She had suffered from lower back pain and radiating pain on the right lower leg for a year and 4 months and so had spine surgery 8 months ago. But the right thigh pain persisted, and the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) remained abnormal. Right femur radiographs showed cortical thickening on the proximal femur. Magnetic resonance images showed T2 hypersignal intensity lesions in the proximal femur. Under suspicion of osteoid osteoma or sclerosing osteomyelitis, surgery was performed with biopsy, bone curettage, and drilling. The culture was negative, and the biopsy showed chronic osteomyelitis. Despite surgery, the levels of CRP and ESR still remained abnormal. After using venous antibiotics, the pain subsided and CRP and ESR levels turned to normal. Followed by 6 weeks of oral antibiotics, pain was relieved after 1-year follow-up.
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