Therapeutically Targeting miR-214 in osteogenic cells promotes bone formation in mice with established osteoporosis induced by ovariectomy

Introduction: Emerging evidence indicates that microRNAs play an important role in regulating osteogenic differentiation and osteoblastic bone formation. But, it has been still lack of miRNAs specifically identified in bone specimens from skeletal disorders with reduced bone formation. In the past years, we have screened miRNAs in bone specimens from fractured postmenopausal women across age and ovariectomized mice during bone loss. Then, we found that miR-214 negatively correlated with reduced bone formation in the examined specimens, implying an inhibition effect of miR214 on osteogenic cell-mediated osteogenesis during age-related reduction in bone formation among postmenopausal women. We used miRBase to predict the targets of miR-214 in mammals. Among the predicted target genes, we focused on ATF4 because it was one of the key transcription factors involved in osteogenesis. Recently, we have developed a targeted delivery system for nucleic acid specifically approaching osteogenic cells at various differentiation stages (Zhang G, et al. Nature Medicine 2011), which facilitated examining the following hypothesis that therapeutically targeting miR-214 in osteogenic cells might promote bone formation in mice with established osteoporosis induced by ovariectomy.