The soybean isoflavone genistein induces differentiation of MG63 human osteosarcoma osteoblasts

A soybean-rich diet has been shown to reduce the incidence of osteoporosis in eastern countries and its effect on bone metabolism ascribed to the action of the soybean isoflavones such as genistein. Although many studies have shown an isoflavone-induced osteoblasts differentiation, its preventative action upon bone mass loss has not been clarified. Here, the osteogenetic effects of genistein on human cell line MG63 osteoblasts were elucidated using a variety of approaches. In particular, phalloidin-rhodamine staining revealed that genistein-treated osteoblasts possessed a more organised cytoskeleton and its inhibitory effect upon cell proliferation was associated with exposure of phosphatidylserines on the external plasmalemma surface. Although this phosphatidylserine exposure is considered a typical apoptotic marker, scanning and transmission electron microscopy revealed that genistein-treated osteoblasts released matrix vesicles and showed no evidence of chromatin condensation. Assays, stainings, and scanning electron microscopy showed that treated osteoblasts synthesised relatively high levels of collagen and alkaline phosphatase and, even in a non-osteogenic growth medium, formed mineralized bone noduli. A clear pattern of genistein-induced osteoblast activation therefore emerges, where all the essential components required for rapid production of mineralised bone extracellular matrix are stimulated by this soybean isoflavone.