Androgens promote preosteoblast differentiation via activation of the canonical Wnt signaling pathway.

Although androgens stimulate bone formation the precise events underlying these effects have not been elucidated. Wnt signaling plays a central role in osteoblast development and bone formation. We demonstrated that dihydrotestosterone (DHT) significantly stimulates MC3T3 preosteoblast differentiation with no effect on cell growth. This effect of DHT was accompanied by increased Wnt signaling in the same cells. Moreover, the stimulatory effects of DHT on preosteoblast differentiation were inhibited by overexpression of soluble frizzed-related protein (sFRP), a naturally occurring Wnt antagonist. These results suggest that androgens promote preosteoblastic differentiation via effects on the canonical Wnt signaling pathway.