mTORC1 and STAT3 signalings are indispensable for in vitro TGFβ1-dependent Three-Dimensional (3D) tendon construct.

The Transforming Growth Factor-{beta} 1 (TGF{beta}1) is a well-known growth factor involved in tenocytes differentiation, extracellular matrix production, and cell fate regulation. We previously demonstrated that TGF{beta}1 has a critical role in the formation of in vitro 3D tendon constructs using mouse primary tendon cells. In this study, we investigated the function of Mammalian target of rapamycin complex 1 (mTORC1) and Signal transducer and activator of transcription 3 (STAT3) signaling in the formation of TGF{beta}1-induced in vitro 3D tendon constructs using specific inhibitors, rapamycin (mTORC1 inhibitor) and stattic (stat3 inhibitor). TGF{beta}1 treatment activated both mTORC1 and STAT3 in 3D tendon constructs. The treatment of rapamycin or stattic partly attenuated TGF{beta}1-dependent cellular, molecular, and matrix changes in the 3D tendon constructs. Overall, this study demonstrates that mTORC1-STAT3 signaling axis is a downstream mediator of TGF{beta}1 signaling in the formation of 3D tendon constructs.