Fig. 9.

Proposed model of TSC1 regulation on the balance between osteoblast and adipocyte differentiation in BMSCs. (A) When TSC1 is present, TSC1-TSC2 complex inhibits mTORC1 activity; PAS develops into autophagosome, which degrades Notch1. In the presence of sufficient β-catenin/Wnt signaling, BMSCs preferentially differentiate into osteoblasts. (B) When TSC1 is deleted, mTORC1 activity is upregulated, which in turn inhibits the autophagosome formation and autophagy-mediated Notch1 degradation. Increased Notch1 can mediate the β-catenin degradation through lysosomal degradation.⁽³⁷⁾ In the absence of sufficient β-catenin/Wnt signaling, BMSCs preferentially differentiate into adipocytes. PAS = pre-autophagosomal structure.