2481-PUB: Oncostatin M Is Involved in Skeletal Muscle Atrophy via the STAT3 Pathway
Authors: MIKI YUYA , MORIOKA TOMOAKI , SHIOI ATSUSHI , SAKURA TAKESHI , KAKUTANI YOSHINORI , FUJIMOTO KENTA , UEDONO HIDEKI , MORI KATSUHITO , SHOJI TETSUO , EMOTO MASANORI , INABA MASAAKI 
Published: June 2019

Recent clinical evidences indicate that sarcopenia is closely related to obesity, type 2 diabetes and atherosclerosis, and mortality risk as well. It has been demonstrated that oncostatin M (OSM), a member of the interleukin-6 family of cytokines, is produced in the adipose tissue and that it promotes adipose tissue inflammation and insulin resistance in obesity. However, the role of OSM in the regulation of skeletal muscle mass remains unknown. In this study, we investigated the effect of OSM on myotube formation of differentiated C2C12 cells in vitro. After C2C12 myoblasts were differentiated into myotubes by a differentiation medium for 72 hours, C2C12 myotubes were treated with OSM for 12 to 48 hours. The diameters of differentiated C2C12 myotubes were reduced by 18.7% and 23.3% compared to the control cells by the treatment with OSM for 24 and 48 hours, respectively. The mRNA expression levels of OSM receptor, atrogin-1, myostatin, and C/EBPδ were significantly increased by 24 hour-treatment with OSM compared to the control cells; while those of myogenin and MyoD were decreased. Moreover, the protein expression of atrogin-1 was increased, myogenin protein level was decreased. Furthermore, OSM phosphorylated STAT3 in differentiated myotubes at 12 and 24 hours. Finally, the inhibitory effect of OSM on the diameter of myotubes was significantly attenuated by the pretreatment with STAT3 inhibitor (C188-9) or by STAT3 knockdown. These in vitro data indicate that OSM contributes to the atrophy of C2C12 myotubes not only by promoting muscle degradation, but also by inhibiting myogenesis via the STAT3 pathway. This study suggests that OSM may regulate skeletal muscle mass in metabolic disorders such as type 2 diabetes.

Disclosure
Y. Miki: None. T. Morioka: Research Support; Self; Eli Lilly and Company, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Roche Diagnostics K.K., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Other Relationship; Self; Ono Pharmaceutical Co., Ltd. A. Shioi: None. T. Sakura: None. Y. Kakutani: None. K. Fujimoto: None. H. Uedono: None. K. Mori: Speaker's Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. T. Shoji: Research Support; Self; Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd. Speaker's Bureau; Self; Kissei Pharmaceutical Co., Ltd., Kowa, Kyowa Hakko Kirin Co., Ltd. M. Emoto: Research Support; Self; Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical CO., Ltd., Takeda Pharmaceutical Company Limited. M. Inaba: None.