mTORC1 and STAT3 signalings are indispensable for in vitro TGFβ1-dependent Three-Dimensional (3D) tendon construct
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The Transforming Growth Factor-β 1 (TGFβ1) is a well-known growth factor involved in tenocytes differentiation, extracellular matrix production, and cell fate regulation. We previously demonstrated that TGFβ1 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 TGFβ1-induced in vitro 3D tendon constructs using specific inhibitors, rapamycin (mTORC1 inhibitor) and stattic (stat3 inhibitor). TGFβ1 treatment activated both mTORC1 and STAT3 in 3D tendon constructs. The treatment of rapamycin or stattic partly attenuated TGFβ1-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 TGFβ1 signaling in the formation of 3D tendon constructs.
