Bone Abstracts

Uncarboxylated osteocalcin, allegedly via G-protein coupled receptors, interacts with adipocytes and pancreatic β-cells, thus affecting metabolic homeostasis. Here, we demonstrate that MK-7 directly and indirectly, via osteocalcin, modulates the endocrine functions of both β-cells and adipocytes.

• It was shown (by applying the Mir@nt@n-based emulation algorithm) that MK-7 was involved in a network of intracellular regulatory loops comprising osteoblast specific microRNAs and transcription factors, including miR-760 targeting SXR. Furthermore, it was demonstrated that MK-7, in the absence or presence of osteoclasts differentiated from human PBMCs, stimulated the secretion of osteocalcin, OPG, RANKL, and interleukins from bovine bone osteoblasts, while anti-SXR siRNA or premiR-760 did the opposite.

• MK-7 enhanced the secretion of adiponectin from adipocytes and insulin (basal and glucose/BCAA-stimulated) from β-cells differentiated from adipose tissue derived stem cells (ASCs). This effect of MK-7 was blocked by adding anti-SXR siRNA or premiR-760 to the cell cultures.

• Adipocytes and β-cells were incubated in preconditioned medium from bovine bone chips obtained in the presence of osteoclasts derived from PBMCs, and in the absence or presence of osteocalcin antibodies, in order to establish their response to G-protein mediated signalling (intracellular cAMP and IP₃ levels). Subsequently, the cells were exposed to siRNAs against G_αs, G_αq, and G_αi2 in the absence or presence of MK-7 showing that: i) osteocalcin affects the G-protein coupled receptors and their intracellular signalling molecules with a certain degree of plasticity; ii) MK-7 is able to modulate this plasticity, while also stimulating egress of secretagogues from the adipocytes and β-cells respectively.

From the present experiments, it appears that vitamin K2 (MK-7) exerts strong direct and indirect hormone-like effects on inter-organ cross-talk, and may represent a key modulator of bone health, as well as energy metabolism.