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骨形成中的长链非编码RNA:关键调节因子与治疗前景

Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects.

作者信息

Jiang Chun, Wang Peng, Tan ZhenWei, Zhang Yin

机构信息

Department of Orthopedics, The People's Hospital of SND, Suzhou, Jiangsu, 215129, China.

Department of Spine Surgery, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, China.

出版信息

Open Life Sci. 2024 Aug 16;19(1):20220908. doi: 10.1515/biol-2022-0908. eCollection 2024.


DOI:10.1515/biol-2022-0908
PMID:39156986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11330173/
Abstract

Recent scientific investigations have revealed the intricate mechanisms underlying bone formation, emphasizing the essential role of long non-coding RNAs (lncRNAs) as critical regulators. This process, essential for skeletal strength and functionality, involves the transformation of mesenchymal stem cells into osteoblasts and subsequent deposition of bone matrix. lncRNAs, including HOX transcript antisense RNA (HOTAIR), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), differentiation antagonizing non-coding RNA (DANCR), and maternally expressed gene 3 (MEG3), have emerged as prominent players in this regulatory network. HOTAIR modulates osteoblast differentiation by interacting with chromatin-modifying enzymes, while MALAT1 regulates osteogenic differentiation through microRNA interactions. DANCR collaborates with Runx2 to fine-tune osteoblast differentiation, and MEG3 orchestrates multiple signaling pathways crucial for bone formation. Moreover, other lncRNAs such as H19, lncRNA for enhancing osteogenesis 3, rhabdomyosarcoma 2-associated transcript, urothelial cancer associated 1, taurine up-regulated gene 1, and nuclear enriched abundant transcript 1 contribute to the complex regulatory network governing osteoblast activities. Understanding the precise roles of these lncRNAs offers promising avenues for developing innovative therapeutic strategies targeting bone-related disorders like osteoporosis. Overall, this review summarizes the pivotal role of lncRNAs in bone formation, highlighting their potential as targets for future research endeavors aimed at advancing therapeutic interventions in bone diseases.

摘要

近期的科学研究揭示了骨形成背后的复杂机制,强调了长链非编码RNA(lncRNAs)作为关键调节因子的重要作用。这一过程对于骨骼强度和功能至关重要,涉及间充质干细胞向成骨细胞的转变以及随后骨基质的沉积。包括HOX转录本反义RNA(HOTAIR)、转移相关肺腺癌转录本1(MALAT1)、分化拮抗非编码RNA(DANCR)和母源表达基因3(MEG3)在内的lncRNAs已成为这一调控网络中的重要参与者。HOTAIR通过与染色质修饰酶相互作用来调节成骨细胞分化,而MALAT1则通过与微小RNA相互作用来调节成骨分化。DANCR与Runx2协同作用以微调成骨细胞分化,MEG3则协调对骨形成至关重要的多种信号通路。此外,其他lncRNAs,如H19、增强成骨作用的lncRNA 3、横纹肌肉瘤2相关转录本、尿路上皮癌相关1、牛磺酸上调基因1和核富集丰富转录本1,也参与了调控成骨细胞活动的复杂网络。了解这些lncRNAs的确切作用为开发针对骨质疏松症等骨相关疾病的创新治疗策略提供了有前景的途径。总的来说,这篇综述总结了lncRNAs在骨形成中的关键作用,突出了它们作为未来研究靶点的潜力,旨在推进骨疾病的治疗干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/1454d2916123/j_biol-2022-0908-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/f0ec9518c702/j_biol-2022-0908-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/26f17d649b80/j_biol-2022-0908-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/2efa2a987217/j_biol-2022-0908-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/1454d2916123/j_biol-2022-0908-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/f0ec9518c702/j_biol-2022-0908-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/26f17d649b80/j_biol-2022-0908-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/2efa2a987217/j_biol-2022-0908-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5d/11330173/1454d2916123/j_biol-2022-0908-fig004.jpg

相似文献

[1]
Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects.

Open Life Sci. 2024-8-16

[2]
Long non-coding RNAs: From disease code to drug role.

Acta Pharm Sin B. 2021-2

[3]
Our emerging understanding of the roles of long non-coding RNAs in normal liver function, disease, and malignancy.

JHEP Rep. 2020-9-3

[4]
Long non-coding RNAs: a new frontier in the study of human diseases.

Cancer Lett. 2013-6-18

[5]
An Overview of Long Noncoding RNAs Involved in Bone Regeneration from Mesenchymal Stem Cells.

Stem Cells Int. 2018-1-28

[6]
Identification of functional lncRNAs based on competing endogenous RNA network in osteoblast differentiation.

J Cell Physiol. 2019-9-4

[7]
LncRNA MALAT1 sponges miR-30 to promote osteoblast differentiation of adipose-derived mesenchymal stem cells by promotion of Runx2 expression.

Cell Tissue Res. 2018-12-3

[8]
Comprehensive analysis of lncRNA-miRNA-mRNA networks during osteogenic differentiation of bone marrow mesenchymal stem cells.

BMC Genomics. 2022-6-7

[9]
Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance.

Int J Mol Sci. 2021-7-6

[10]
Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells.

Stem Cell Res Ther. 2017-2-7

引用本文的文献

[1]
A miR-30 Guided Molecular Profiling of Canine Osteosarcoma and Extraskeletal Osteosarcoma Reveals Non-Seed Regulatory Divergence.

Cells. 2025-8-18

[2]
Deciphering the etiology of congenital scoliosis: A genetic and epigenetic perspective.

World J Orthop. 2025-6-18

[3]
Involvement of long non-coding RNA (lncRNA) MALAT1 in shear stress regulated adipocyte differentiation.

Front Bioeng Biotechnol. 2025-5-6

本文引用的文献

[1]
Exosomal Lnc NEAT1 from endothelial cells promote bone regeneration by regulating macrophage polarization via DDX3X/NLRP3 axis.

J Nanobiotechnology. 2023-3-20

[2]
LncRNA MALAT1 mediates osteogenic differentiation in osteoporosis by regulating the miR-485-5p/WNT7B axis.

Front Endocrinol (Lausanne). 2022

[3]
Long non-coding RNAs: definitions, functions, challenges and recommendations.

Nat Rev Mol Cell Biol. 2023-6

[4]
Author Correction: Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics.

Nat Rev Mol Cell Biol. 2022-12

[5]
A novel ceRNA regulatory network involving the long noncoding NEAT1, miRNA-466f-3p and its mRNA target in osteoblast autophagy and osteoporosis.

J Mol Med (Berl). 2022-11

[6]
The mechanosensitive lncRNA Neat1 promotes osteoblast function through paraspeckle-dependent Smurf1 mRNA retention.

Bone Res. 2022-2-24

[7]
Long non-coding RNA TUG1 knockdown repressed the viability, migration and differentiation of osteoblasts by sponging miR-214.

Exp Ther Med. 2022-3

[8]
Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics.

Nat Rev Mol Cell Biol. 2022-6

[9]
Downregulation of the LncRNA MEG3 Promotes Osteogenic Differentiation of BMSCs and Bone Repairing by Activating Wnt/β-Catenin Signaling Pathway.

J Clin Med. 2022-1-13

[10]
The management of bone defect using long non-coding RNA as a potential biomarker for regulating the osteogenic differentiation process.

Mol Biol Rep. 2022-3

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