Fig. 7. Schematic representation of AMPK-mediated RUNX2 regulation and its mechanism in differentiation.

The schematic mechanism representing the molecular insights of multipotent MSCs differentiation of osteogenesis vs adipogenesis. AMPK is a physiological sensor and regulates energy homeostasis through multiple intermediates. Under altered metabolic conditions, such as hyperglycemia, with reduced active AMPK favors adipogenesis. The homeostasis in differentiation of osteogenesis vs adipogenesis is due to regulation of RUNX2, which is known to be a master regulator of osteogenesis. This regulation is maintained by phosphorylation of RUNX2-S118, by stabilizing its protein levels from proteosomal degradation (ubiquitination). This could be a plausible phenomenon, where AMPK activators such as metformin etc. are shown to have healthy bones, especially under metabolic stress conditions such as diabetes