Sci Rep. 2025 Jul 1;15(1):20687.doi: 10.1038/s41598-025-05826-z.

本文采用的英格恩产品: DNA-Entranster-invivo, Entranster-H4000, RNA-Entranster-invivo, 体内转染

中文解读

CTD-2555A7.2 通过其重复序列结合多个 miR-381-3p 分子,从而促进骨形成。miR-381-3p 通过同时靶向 Wnt 信号通路的四个关键基因 Apc、Lef1、wnt5a 和 Lrp6,抑制成骨分化。

本研究中英格恩产品的用法:体外质粒转染:使用 Engreen Entranster™ H4000 Reagent(4000-6,Engreen Biosystem Co, Ltd., Beijing, China)进行质粒转染,按产品提供的操作方案执行。依据中未给出本实验的具体核酸用量、细胞密度和检测时间点,这里不代作者补充;如需按孔板规格换算用量,可参考转染试剂选型指南。

阅读完整中文解读 →

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

Affiliations

Affiliations

  • 1 School of Laboratory Medicine, Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
  • 2 Department of Clinical Laboratory, Lab of Nucleic Acid Therapy, Department of Oncology, Department of Rehabilitation Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
  • 3 School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
  • 4 National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, 650000, China.
  • 5 Department of Clinical Laboratory, Lab of Nucleic Acid Therapy, Department of Oncology, Department of Rehabilitation Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China. beileizeng@126.com.
  • 6 Department of Oncology, Affiliated Hospital of North Sichuan Medical College, 1 # Maoyuan South Road, Nanchong City, 637000, Sichuan Province, China. beileizeng@126.com.
  • 7 College of Basic Medicine, Beihua University, Jilin, 132000, Jilin, China. yangchun1949@163.com.
  • 8 College of Basic Medicine, Beihua University, 3999 # Binjiang East Road, Jilin City, 132000, Jilin Province, China. yangchun1949@163.com.
  • 9 Department of Cell Biology, College of Basic Medical Sciences, Tianjin Medical University, 22 # Qixiangtai Road, Heping District, Tianjin, 300070, China. yang.bing@krirk.ac.th.
  • 10 Department of Public Health, International School, Krirk University, 3 # Soi Ramintra 1 Anusawari Subdistrict, Bang Khen District, Bangkok, 10220, Thailand. yang.bing@krirk.ac.th.
  • 11 Department of Clinical Laboratory, Lab of Nucleic Acid Therapy, Department of Oncology, Department of Rehabilitation Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China. yinchong42@nsmc.edu.cn.
  • 12 School of Laboratory Medicine, Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637000, Sichuan, China. yinchong42@nsmc.edu.cn.
  • 13 Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, 1 # Maoyuan South Road, Nanchong City, 637000, Sichuan Province, China. yinchong42@nsmc.edu.cn.

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.

Keywords: Bone formation; LncRNA CTD-2555A7.2; MiR-381-3p; Osteogenic differentiation; Osteoporosis.

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