CTD-2555A7.2 promotes bone formation with LncRNA-specific cascade amplification strategy

Abstract Osteoporosis is a potential threat to human health. LncRNAs have been deem as important regulators for the pathogenesis of osteoporosis. However, the accuracy and efficiency of LncRNA regulating bone formation still need to be improved. We previously found a repeat sequence on human-derived LncRNA CTD-2555A7.2, implying it may potentially regulate osteoporosis more efficiently. Therefore, we deeply analyzed the function of LncRNA CTD-2555A7.2 on bone formation and further investigated its mechanism and its potential to rescue osteoporosis. Our research demonstrated that CTD-2555A7.2 promoted bone formation through sequestering with multiple miR-381-3p molecules via its repeat sequence. miR-381-3p inhibited osteogenic differentiation by simultaneously targeting 4 essential genes in the wnt signaling pathway, including Apc, Lef1, wnt5a, and Lrp6. The repeat sequence of CTD-2555A7.2 presented a significant therapeutic effect on osteoporosis. Taken together, we identified a dual amplification osteogenic axis CTD-2555A7.2-miR-381-wnt showed a significant regulating effect on osteoporosis. This study laid an important theoretical and experimental foundation to investigate the mechanism of osteogenic-related LncRNAs and also provided novel insights for developing therapeutic drugs for osteoporosis.