The soybean isoflavone genistein induces differentiation of MG63 human osteosarcoma osteoblasts

A soybean-rich diet was shown to reduce the incidence of osteoporosis in Eastern countries; its effect on bone metabolism was ascribed to the action of the soybean isoflavones such as genistein. Although many studies have shown isoflavone-induced osteoblast differentiation, its preventative action on 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 organized cytoskeleton, and genistein's 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 genistein-treated osteoblasts synthesized relatively high levels of collagen and alkaline phosphatase and, even in a nonosteogenic growth medium, formed mineralized bone noduli. A clear pattern of genistein-induced osteoblast activation therefore emerges, in which all of the essential components required for the rapid production of mineralized bone extracellular matrix are stimulated by this soybean isoflavone.