Fig. 8. Molecular control of spatiotemporal cues for synergistic intracellular signaling.
Description of molecular events occurring after simultaneous NaBC1/α5β1/αvβ3 and NaBC1/BMPR1A activation. FN stimulate FN-binding integrins while borax stimulates the NaBC1 transporter. NaBC1 co-localizes with FN-binding integrins and BMPR1A, thus cooperating and stimulating downstream pathways controlling MSCs fate. Note that this cooperation does not necessarily implies a physical interaction. Canonical BMPR1A activation concludes in Smad1 phosphorylation, inducing osteogenesis via OPN expression. After activation, both (NaBC1 and FN-binding integrins) receptors induce the formation of large focal adhesions, resulting in high intracellular tension that derive into nuclear stress and YAP translocation to the nucleus inducing osteogenesis. High mechanical tension activates ERK, which inhibits adipogenesis after phosphorylation.