Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays a role in various disorders such as cancer and inflammatory diseases, which are often accompanied by skeletal muscle atrophy, or sarcopenia. However, the role of OSM in the regulation of skeletal muscle mass remains to be identified. In this study, we investigated the effect of OSM on C2C12 myotube formation in vitro. C2C12 myoblasts were induced to differentiate into myotubes for 3 days and then treated with OSM for 24 or 48 h. The diameter of differentiated C2C12 myotubes were reduced by 18.7% and 23.3% compared to control cells after treatment with OSM for 24 and 48 h, respectively. The expression levels of MyoD and myogenin were decreased, while those of atrogin-1, CCAAT/enhancer binding protein 8, and OSM receptor were increased in C2C12 myotubes treated with OSM for 24 h compared to control cells. Furthermore, the inhibitory effect of OSM on myotube formation was significantly attenuated by pretreatment with an inhibitor of signal transducer and activator of transcription (STAT) 3 or by knockdown of Stat3. Finally, the OSM-induced changes in the expression levels of MyoD, myogenin, and atrogin-1 were reversed by pretreatment with an inhibitor of STAT3 or by Stat3 knockdown in C2C12 myotubes. In conclusion, OSM induces C2C12 myotube atrophy by inhibiting myogenic differentiation and activating muscle degradation in a STAT3-dependent manner. (C) 2019 Elsevier Inc. All rights reserved.