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levels. Interestingly, the divalent cations alone did not influence osteogenesis and aerobic glycolysis of undifferentiated MSCs. However, once the osteogenic differentiation of MSCs was initiated by neurotransmitters or osteogenic differentiation medium, the osteogenesis of MSCs could be significantly promoted by the divalent cations, which was accompanied by the improved aerobic glycolysis. In terms of indirect effects, the divalent cations significantly upregulated levels of sensory nerve derived CGRP, PNS produced choline acetyltransferase and type H vessels, while significantly tuned down sympathetic activity in the defect zone in rats, thereby contributing to significantly increased bone formation relative to the control group. Together, the divalent cations favor bone regeneration via modulation of sensory-autonomic nervous systems and promotion of aerobic glycolysis-driven osteogenesis of MSCs after osteogenic initiation by neurotransmitters.
Luo et al. (Wed,) studied this question.