The bone anabolic carotenoid beta-cryptoxanthin enhances transforming growth factor-beta1-induced SMAD activation in MC3T3 preosteoblasts.

The xanthophyll beta-cryptoxanthin is a member of the carotenoid family of plant-derived pigments endowed with anti-osteoporotic properties in vivo. beta-cryptoxanthin was demonstrated to stimulate osteoblastic bone formation and simultaneously repress osteoclastic bone resorption in vitro. However, the mechanisms of action remain to be elucidated. The SMAD signal transduction pathway is established to play a critical role in osteoblast lineage commitment and differentiation. In this study we used transient transfection assays of a SMAD luciferase reporter to investigate whether beta-cryptoxanthin regulates SMAD activation in MC3T3 pre-osteoblastic cells. Beta-cryptoxanthin did not stimulate basal SMAD activity but amplified transforming growth factor (TGF)-beta1-induced SMAD activation. Interestingly, beta-cryptoxanthin did not affect bone morphogenetic protein-2 (BMP-2)-induced SMAD activation in osteoblastic cells, suggesting specificity of action on the TGF-beta1 pathway. This study suggests that the carotenoid beta-cryptoxanthin may promote osteoblast differentiation and activity by amplifying TGF-beta1-induced lineage commitment of osteoblast precursors.