文章基本信息

标题：mTORC1 Overactivation Leads to Abnormalities in Skeletal Development
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作者：Sayuki Iwahashi ; Kazuya Tokumura ; Gyujin Park 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2020
卷号：43
期号：12
页码：1983-1986
DOI：10.1248/bpb.b20-00619
出版社：The Pharmaceutical Society of Japan
摘要：The mechanistic/mammalian target of rapamycin complex-1 (mTORC1) integrates multiple signaling pathways and regulates various cellular processes. Tuberous sclerosis complex 1 ( Tsc1 ) and complex 2 ( Tsc2 ) are critical negative regulators of mTORC1. Mouse genetic studies, including ours, have revealed that inactivation of mTORC1 in undifferentiated mesenchymal cells and chondrocytes leads to severe skeletal abnormalities, indicating a pivotal role for mTORC1 in skeletogenesis. Here, we show that hyperactivation of mTORC1 influences skeletal development through its expression in undifferentiated mesenchymal cells at the embryonic stage. Inactivation of Tsc1 in undifferentiated mesenchymal cells by paired-related homeobox 1 ( Prx1 )- Cre -mediated recombination led to skeletal abnormalities in appendicular skeletons. In contrast, Tsc1 deletion in chondrocytes using collagen type II α1 ( Col2a1 )- Cre or in osteoprogenitors using Osterix ( Osx ) -Cre did not result in skeletal defects in either appendicular or axial skeletons. These findings indicate that Tsc complex-mediated chronic overactivation of mTORC1 influences skeletal development at the embryonic stage through its expression in undifferentiated mesenchymal cells but not in chondrocytes or osteoprogenitors.
关键词：skeletogenesis;undifferentiated mesenchymal cell;tuberous sclerosis complex 1;mechanistic/mammalian target of rapamycin complex-1 (mTORC1)