Differential response of MC3T3-E1 and human mesenchymal stem cells to inositol hexakisphosphate.

BACKGROUND Inositol hexakisphosphate (IP6) has been found to have an important role in biomineralization. METHODS Because the complete mechanism of action of IP6 on osteoblasts is not fully understood and its potential use in the primary prevention of osteoporosis, we examined the direct effect of IP6 on cell viability and differentiation of MC3T3-E1 cells and on differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). RESULTS We show that IP6 has different effects depending on the origin of the cell target. Thus, while IP6 decreased gene expression of osteoblast markers and mineralization in MC3T3-E1 cells without negatively affecting cell viability and ALP activity, an increase in gene expression of ALP was observed in hUC-MSCs committed to the osteoblastic lineage. This increasing effect of IP6 on ALP mRNA expression levels was reversed by the addition of a selective inhibitor of IP6 kinase, suggesting that the effect of IP6 might be due through its pyrophosphorylated derivatives. Besides, Rankl mRNA levels were decreased after IP6 treatment in MC3T3-E1 cells, pointing to a paracrine effect on osteoclasts. CONCLUSION Our results indicate that IP6 has different effects on osteoblast differentiation depending on the cell type and origin. However, further studies are needed to examine the net effect of IP6 on bone formation and its potential as novel antiosteoporosis drug.