High glutamine suppresses osteogenesis through mTORC1-mediated inhibition of the mTORC2/AKT-473/RUNX2 axis.

ABSTRACT: Activation of the key nutrient cellular sensors mTORC1 and mTORC2 directs the fate of mesenchymal stromal cells (MSCs). Here, we report that glutamine regulates crosstalk between mTOR complexes and lineage commitment of MSCs independent of glucose concentration. High glutamine-induced mTORC1 hyperactivation resulted in the suppression of mTORC2, which otherwise stabilizes RUNX2 via GSK3β inhibition through pAKT-473. Activation of GSK3β resulted in the ubiquitination of RUNX2, a key transcription factor for the osteogenic commitment of MSCs. However, low glutamine conditions inhibit mTORC1 hyperactivation followed by increased mTORC2 activation and RUNX2 stabilization. Under diabetic/high-glucose conditions, glutamine-triggered hyperactivation of mTORC1 resulted in mTORC2 suppression, and a

SUBMITTER: Gayatri MB 

PROVIDER: S-EPMC9174279 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature