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

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

Abstract Osteoporosis poses a significant threat to human health. Long non-coding RNAs (LncRNAs) have been deemed as crucial regulators in the pathogenesis of osteoporosis. However, the accuracy and efficiency of LncRNA-mediated regulation of bone formation require further improvement. Our previous...

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Main Authors: Fanjin Meng, Kaiyuan Zheng, Meng Deng, Yuwen Ma, Yang Yu, Junxiong Li, Hong Chen, Shan Meng, Bin Guo, Xiaolan Guo, Li Jiao, Beilei Zeng, Chun Yang, Bing Yang, Chong Yin
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Osteoporosis
LncRNA CTD-2555A7.2
Bone formation
Osteogenic differentiation
MiR-381-3p
Online Access:https://doi.org/10.1038/s41598-025-05826-z
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Summary:Abstract Osteoporosis poses a significant threat to human health. Long non-coding RNAs (LncRNAs) have been deemed as crucial regulators in the pathogenesis of osteoporosis. However, the accuracy and efficiency of LncRNA-mediated regulation of bone formation require further improvement. Our previous study identified a repeat sequence in the human-derived LncRNA CTD-2555A7.2, suggesting its potential role in osteoporosis regulation. To investigate this hypothesis, we conducted systematic functional analyses of CTD-2555A7.2 in osteogenesis and explored its mechanisms and potential therapeutic applications. Through over-expression, siRNA silencing and repeat sequence over-expression in vitro and in vivo, our research demonstrate that CTD-2555A7.2 enhances bone formation by sequestering multiple miR-381-3p molecules through its repeat sequence. Through Western blot, siRNA silencing and luciferase reporter assay, we illuminated miR-381-3p suppresses osteogenic differentiation by concurrently targeting four essential genes of the Wnt signaling pathway: Apc, Lef1, wnt5a, and Lrp6. Notably, the mRNA of CTD-2555A7.2 repeat sequence exhibited pronounced therapeutic efficacy in ovariectomy osteoporosis models. Taken together, we identified a dual-amplification osteogenic axis (CTD-2555A7.2-miR-381-Wnt) that demonstrates significant regulatory effects on osteoporosis. This study has established an important theoretical framework for understanding osteogenic LncRNA mechanisms and provides novel insights for developing targeted therapeutics against osteoporosis.
ISSN:2045-2322

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