Osteoporosis has become a high incident
bone disease along with the aging of human population. Long noncoding RNAs (LncRNAs) play an important role in
osteoporosis incidence. In this study, we screened out an
LncRNA negatively correlated with osteoblast differentiation, which was therefore named Lnc-DIF (differentiation inhibiting factor). Functional analysis proved that Lnc-DIF inhibited bone formation. A special structure containing multiple 53
nucleotide repeats was found in the trailing end of Lnc-DIF. Our study suggested that this repeat sequence could sequester multiple miR-489-3p and inhibit bone formation through miR-489-3p/SMAD2 axis. Moreover,
siRNA of Lnc-DIF would rescue bone formation in both aging and ovariectomized
osteoporosis mice. This study revealed a kind of
LncRNA that could function as a sponge and regulate multiple
miRNAs.
RNA therapy techniques that target these LncRNAs could manipulate its downstream
miRNA-target pathway with significantly higher efficiency and specificity. This provided potential therapeutic insight for
RNA-based
therapy for
osteoporosis.