mTOR signaling in skeletal development and disease

Abstract

The mammalian/mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that integrates inputs from nutrients and growth factors to control many fundamental cellular processes through two distinct protein complexes mTORC1 and mTORC2. Recent mouse genetic studies have established that mTOR pathways play important roles in regulating multiple aspects of skeletal development and homeostasis. In addition, mTORC1 has emerged as a common effector mediating the bone anabolic effect of Igf1, Wnt and Bmp. Dysregulation of mTORC1 could contribute to various skeletal diseases including osteoarthritis and osteoporosis. Here we review the current understanding of mTOR signaling in skeletal development and bone homeostasis, as well as in the maintenance of articular cartilage. We speculate that targeting mTOR signaling may be a valuable approach for treating skeletal diseases.

Skeletal development: Regulatory pathway offers drug target for bone disease

Drugs directed at a key cellular signaling pathway could prove useful for treating skeletal diseases. Jianquan Chen from Soochow University in Suzhou, China, and Fanxin Long from Washington University School of Medicine in St. Louis, Missouri, USA, provide an overview of how proteins involved in the mechanistic target of rapamycin (mTOR) signaling pathway sense and integrate a range of environmental cues to regulate bone and cartilage development. In particular, they review the differing roles of the two distinct mTOR-containing protein complexes, mTORC1 and mTORC2. Both seem to mediate bone formation and resorption but in different ways, with implications for how best to treat osteoarthritis, osteoporosis, and other degenerative skeletal diseases. The authors suggest that more specific mTOR inhibitors with minimal side effects are needed to help stimulate bone growth in these diseases.

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