Fat Mass and Obesity-Associated (FTO) Stimulates Osteogenic Differentiation of C3H10T1/2 Cells by Inducing Mild Endoplasmic Reticulum Stress via a Positive Feedback Loop with p-AMPK.

作者: Won-Gu Jang , Eun-Jung Kim , Eun-Jung Kim , Hyeon-Young Min , Hyo-Eun Son

DOI: 10.14348/MOLCELLS.2019.0136

关键词:

摘要: Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling expenditure. In addition, FTO functions the regulation of obesity adipogenic differentiation; however, a role osteogenic differentiation is unknown. This study investigated effects on C3H10T1/2 cells underlying mechanism. Expression endoplasmic reticulum (ER) stress markers were characterized reverse-transcriptase polymerase chain reaction western blotting. Alkaline phosphatase (ALP) staining was performed assess ALP activity. BMP2 treatment increased mRNA expression genes FTO. Overexpression distal-less homeobox5 (Dlx5) runt-related transcription factor 2 (Runx2). Activation adenosine monophosphate-activated protein kinase (AMPK) expression, there positive feedback loop between p-AMPK. p-AMPK induced mild ER stress; tunicamycin-induced severe suppressed AMPK activation. summary, induces upon inducing via with activation induce stress. By contrast, inhibits suppressing

参考文章(33)
Akira Yamaguchi, Toshihisa Komori, Tatsuo Suda, Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocrine Reviews. ,vol. 21, pp. 393- 411 ,(2000) , 10.1210/EDRV.21.4.0403
D. Tews, P. Fischer-Posovszky, M. Wabitsch, FTO - Friend or foe? Hormone and Metabolic Research. ,vol. 42, pp. 75- 80 ,(2010) , 10.1055/S-0029-1241831
Jianjin Guo, Wei Ren, Aimei Li, Ying Ding, Wanhua Guo, Dongming Su, Cheng Hu, Kuanfeng Xu, Heng Chen, Xinyu Xu, Tao Yang, Weiping Jia, Fat Mass and Obesity-Associated Gene Enhances Oxidative Stress and Lipogenesis in Nonalcoholic Fatty Liver Disease Digestive Diseases and Sciences. ,vol. 58, pp. 1004- 1009 ,(2013) , 10.1007/S10620-012-2516-6
Tomohiko Murakami, Atsushi Saito, Shin-ichiro Hino, Shinichi Kondo, Soshi Kanemoto, Kazuyasu Chihara, Hiroshi Sekiya, Kenji Tsumagari, Kimiko Ochiai, Kazuya Yoshinaga, Masahiro Saitoh, Riko Nishimura, Toshiyuki Yoneda, Ikuyo Kou, Tatsuya Furuichi, Shiro Ikegawa, Masahito Ikawa, Masaru Okabe, Akio Wanaka, Kazunori Imaizumi, Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation. Nature Cell Biology. ,vol. 11, pp. 1205- 1211 ,(2009) , 10.1038/NCB1963
Yan Guo, Hui Liu, Tie-Lin Yang, Siyang M. Li, Siyuan K. Li, Qing Tian, Yong-Jun Liu, Hong-Wen Deng, The Fat Mass and Obesity Associated Gene, FTO, Is Also Associated with Osteoporosis Phenotypes PLoS ONE. ,vol. 6, pp. e27312- ,(2011) , 10.1371/JOURNAL.PONE.0027312
Umut Ozcan, Qiong Cao, Erkan Yilmaz, Ann-Hwee Lee, Neal N Iwakoshi, Esra Ozdelen, Gurol Tuncman, Cem Görgün, Laurie H Glimcher, Gokhan S Hotamisligil, Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes Science. ,vol. 306, pp. 457- 461 ,(2004) , 10.1126/SCIENCE.1103160
Jianze Li, Brenda Lee, Amy S. Lee, Endoplasmic Reticulum Stress-induced Apoptosis Journal of Biological Chemistry. ,vol. 281, pp. 7260- 7270 ,(2006) , 10.1074/JBC.M509868200
Xu Zhao, Ying Yang, Bao-Fa Sun, Yue Shi, Xin Yang, Wen Xiao, Ya-Juan Hao, Xiao-Li Ping, Yu-Sheng Chen, Wen-Jia Wang, Kang-Xuan Jin, Xing Wang, Chun-Min Huang, Yu Fu, Xiao-Meng Ge, Shu-Hui Song, Hyun Seok Jeong, Hiroyuki Yanagisawa, Yamei Niu, Gui-Fang Jia, Wei Wu, Wei-Min Tong, Akimitsu Okamoto, Chuan He, Jannie M Rendtlew Danielsen, Xiu-Jie Wang, Yun-Gui Yang, FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis Cell Research. ,vol. 24, pp. 1403- 1419 ,(2014) , 10.1038/CR.2014.151
J. S. Oakhill, J. W. Scott, B. E. Kemp, Structure and function of AMP-activated protein kinase. Acta Physiologica. ,vol. 196, pp. 3- 14 ,(2009) , 10.1111/J.1748-1716.2009.01977.X
Jaemin Lee, Umut Ozcan, Unfolded Protein Response Signaling and Metabolic Diseases Journal of Biological Chemistry. ,vol. 289, pp. 1203- 1211 ,(2014) , 10.1074/JBC.R113.534743