Inositol hexakisphosphate reduces bone mineralization and affects body axis formation

Inositol hexakisphosphate (IP6) is a naturally occurring compound found in many plants and is known to prevent soft tissue calcification in mammals. However, the contribution of IP6 to bone mineralization in vivo remains largely unknown. Zebrafish larvae were used to address the effect of exogenous IP6 administration on bone matrix mineralization and embryonic development. IP6 caused a dose-dependent inhibition of vertebrae and craniofacial tissue ossification in zebrafish larvae at concentrations ranging between 100 µg/ml (p = 0.35) and 300 µg/ml (p < 0.0001). Acute toxicity test of IP6 revealed a 50% lethal concentration of 313 ± 41 µg/ml at 4 days post-fertilization. Moreover, IP6 treatment reduced (p < 0.0001) the heartbeats of the embryos at high concentrations (≥ 300 µg/ml) and abolished the development of the tail with a prevalence exceeding 40% (p < 0.0001) after treatment with 350 µg/ml of IP6. We report for the first time the effect of IP6 treatment in the zebrafish model organism. This animal study further supports the previously reported role of IP6 in the differentiation of bone-derived cells and inhibition of bone mineralization. These observations confirm the paradoxical role of the IP6 molecule on bone homeostasis and health.