期刊
STEM CELLS
卷 36, 期 4, 页码 527-539出版社
WILEY
DOI: 10.1002/stem.2765
关键词
Tendon; Tenogenesis; Mechanistic target of rapamycin; AKT; Type I collagen
资金
- Natural Science Foundation of Zhejiang Province [LY13C070002]
- International Science & Technology Cooperation Program of China (the Ministry of Science and Technology of PRC) [2015DFG32130]
- Key Scientific and Technological Innovation Team of Zhejiang Province [2013TD11]
- National Natural Science Foundation of China [31371476, 81330041, 31571402, 31671417, 81572157]
Tendon repair is a clinical challenge because of the limited understanding on tenogenesis. The synthesis of type I collagen (Collagen I) and other extracellular matrix are essential for tendon differentiation and homeostasis. Current studies on tenogenesis focused mostly on the tenogenic transcriptional factors while the signaling controlling tenogenesis on translational level remains largely unknown. Here, we showed that mechanistic target of rapamycin (mTOR) signaling was activated by protenogenic growth factor, transforming growth factors beta1, and insulin-like growth factor-I. The expression of mTOR was upregulated during tenogenesis of mesenchymal stem cells (MSCs). Moreover, mTOR was downregulated in human tendinopathy tissues and was inactivated upon statin treatment. Both inhibition and depletion of AKT or mTOR significantly reduced type I collagen production and impaired tenogenesis of MSCs. Tendon specific-ablation of mTOR resulted in tendon defect and reduction of Collagen I. However, there is no evident downregulation of tendon associated collagens at the transcription level. Our study demonstrated that AKT-mTOR axis is a key mediator of tendon differentiation and provided a novel therapeutic target for tendinopathy and tendon injuries.
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