Emodin accelerates osteoblast differentiation through phosphatidylinositol 3-kinase activation and bone morphogenetic protein-2 gene expression.

Emodin is a naturally occurring anthraquinone present in the roots and bark of numerous plants of the genus Rhamnus. Here, we identified emodin as one of compounds activating the mRNA expression of bone morphogenetic protein (BMP)-2 in the differentiation process of mouse osteoblastic MC3T3-E1 subclone 4 cells. Without any effect on cell growth, the low concentration (up to 5 microM) of emodin highly induced the mRNA expression of BMP-2, the expression of alkaline phosphatase (an early marker of osteoblast differentiation), and the mineralization. Interestingly, emodin induced the activation of phosphatidylinositol 3-kinase (PI3K), Akt and mitogen-activated protein (MAP) kinases, but those inductions by emodin were completely inhibited by the PI3K inhibitor, LY294002, suggesting that the up-regulation of BMP-2 by emodin could be mediated through the activation of both Akt and MAP kinases by activating PI3K. Additionally, emodin-induced activation of NF-kappaB suggested that NF-kappaB might be required for its anabolic activity in part. In conclusion, the use of natural compounds with anabolic activity such as emodin could have a beneficial effect on bone health and this kind of studies further elucidate the pharmacological roles of natural compounds in the prevention of osteoporosis and provide the initiative in the early drug discovery and development for osteoporosis.