Rapamycin improves bone mass in high-turnover osteoporosis with iron accumulation through positive effects on osteogenesis and angiogenesis.

Abstract

Iron accumulation is an independent risk factor for type I osteoporosis, but the molecular mechanisms of the phenomenon are not well defined, and effective therapy has not been reported. Here, we found that the level of mTOR was increased both in wild-type mouse models with iron accumulation and transgenic mouse models (Hepc^-/-) of high-turnover osteoporosis with iron accumulation. We show that an increased level of mTOR can depress osteogenesis and angiogenesis by Cxcl9 both in bone and in vitro. Suppression of mTOR in mouse models by rapamycin and in vitro by siRNA transfection recovered both osteogenesis and angiogenesis. These findings revealed the role of mTOR in osteogenesis and angiogenesis in high-turnover osteoporosis with iron accumulation and showed that rapamycin targeting of mTOR ameliorates osteogenesis and angiogenesis to improve bone mass.