Open AccessActivation of AKT‐mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells
Author(s) -
Cong Xiao Xia,
Rao Xi Sheng,
Lin Jun Xin,
Liu Xiao Ceng,
Zhang Guang An,
Gao Xiu Kui,
He Min Yi,
Shen Wei Liang,
Fan Wei,
Pioletti Dominique,
Zheng Li Ling,
Liu Huan Huan,
Yin Zi,
Low Boon Chuan,
Schweitzer Ronen,
Ouyang Hongwei,
Chen Xiao,
Zhou Yi Ting
Publication year - 2018
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2765
Subject(s) - pi3k/akt/mtor pathway , biology , microbiology and biotechnology , mesenchymal stem cell , protein kinase b , downregulation and upregulation , tendinopathy , stem cell , tendon , cancer research , signal transduction , anatomy , biochemistry , gene
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. S tem C ells 2018;36:527–539