Long noncoding RNA Lnc-DIF inhibits bone formation by sequestering miR-489-3p

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. [Display omitted] •Identified LncRNA Lnc-DIF that inhibited bone formation•Lnc-DIF sequestered multiple miR-489-3p by the repeat sequences on its trailing end•Lnc-DIF repeat sequence inhibited bone formation via miR-489-3p/SMAD2 axis•Lnc-DIF siRNA showed strong capability on rescuing osteoporosis Biological sciences; Molecular biology; Molecular mechanism of gene regulation; Orthopedics