Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells

Autor: Yi Ting Zhou, Xiao Chen, Hongwei Ouyang, Min Yi He, Xiao Ceng Liu, Boon Chuan Low, Zi Yin, Wei Fan, Xiao Xia Cong, Huanhuan Liu, Ronen Schweitzer, Junxin Lin, Dominique P. Pioletti, Guang An Zhang, Xi Sheng Rao, Li Ling Zheng, Wei Liang Shen, Xiu Kui Gao
Rok vydání: 2018
Předmět:
Zdroj: Stem Cells. 36:527-539
ISSN: 1549-4918
1066-5099
DOI: 10.1002/stem.2765
Popis: 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.
Databáze: OpenAIRE
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