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微小RNA-146a通过下调SMAD2和SMAD3来调节人胎儿股骨来源的骨骼干细胞分化。

MicroRNA-146a regulates human foetal femur derived skeletal stem cell differentiation by down-regulating SMAD2 and SMAD3.

作者信息

Cheung Kelvin S C, Sposito Nunzia, Stumpf Patrick S, Wilson David I, Sanchez-Elsner Tilman, Oreffo Richard O C

机构信息

Bone and Joint Research Group, Institute of Developmental Sciences, Southampton General Hospital, Southampton, United Kingdom; Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, University of Southampton, Southampton, United Kingdom.

Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, University of Southampton, Southampton, United Kingdom.

出版信息

PLoS One. 2014 Jun 3;9(6):e98063. doi: 10.1371/journal.pone.0098063. eCollection 2014.

DOI:10.1371/journal.pone.0098063
PMID:24892945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4043645/
Abstract

MicroRNAs (miRs) play a pivotal role in a variety of biological processes including stem cell differentiation and function. Human foetal femur derived skeletal stem cells (SSCs) display enhanced proliferation and multipotential capacity indicating excellent potential as candidates for tissue engineering applications. This study has examined the expression and role of miRs in human foetal femur derived SSC differentiation along chondrogenic and osteogenic lineages. Cells isolated from the epiphyseal region of the foetal femur expressed higher levels of genes associated with chondrogenesis while cells from the foetal femur diaphyseal region expressed higher levels of genes associated with osteogenic differentiation. In addition to the difference in osteogenic and chondrogenic gene expression, epiphyseal and diaphyseal cells displayed distinct miRs expression profiles. miR-146a was found to be expressed by human foetal femur diaphyseal cells at a significantly enhanced level compared to epiphyseal populations and was predicted to target various components of the TGF-β pathway. Examination of miR-146a function in foetal femur cells confirmed regulation of protein translation of SMAD2 and SMAD3, important TGF-β and activin ligands signal transducers following transient overexpression in epiphyseal cells. The down-regulation of SMAD2 and SMAD3 following overexpression of miR-146a resulted in an up-regulation of the osteogenesis related gene RUNX2 and down-regulation of the chondrogenesis related gene SOX9. The current findings indicate miR-146a plays an important role in skeletogenesis through attenuation of SMAD2 and SMAD3 function and provide further insight into the role of miRs in human skeletal stem cell differentiation modulation with implications therein for bone reparation.

摘要

微小RNA（miRs）在包括干细胞分化和功能在内的多种生物学过程中发挥着关键作用。人胎儿股骨来源的骨骼干细胞（SSCs）表现出增强的增殖能力和多能性，这表明其作为组织工程应用候选者具有巨大潜力。本研究检测了miRs在人胎儿股骨来源的SSCs向软骨生成和成骨谱系分化过程中的表达及作用。从胎儿股骨骨骺区域分离的细胞表达了更高水平的与软骨生成相关的基因，而来自胎儿股骨干区域的细胞表达了更高水平的与成骨分化相关的基因。除了成骨和软骨生成基因表达的差异外，骨骺和骨干细胞还表现出不同的miRs表达谱。与骨骺细胞群体相比，发现人胎儿股骨干细胞中miR-146a的表达水平显著增强，并且预测其靶向TGF-β信号通路的各种成分。对胎儿股骨细胞中miR-146a功能的检测证实，在骨骺细胞中瞬时过表达后，miR-146a可调节SMAD2和SMAD3的蛋白质翻译，SMAD2和SMAD3是重要的TGF-β和激活素配体信号转导分子。miR-146a过表达后SMAD2和SMAD3的下调导致成骨相关基因RUNX2的上调和软骨生成相关基因SOX9的下调。目前研究结果表明，miR-146a通过减弱SMAD2和SMAD3的功能在骨骼发生中发挥重要作用，并为miRs在人类骨骼干细胞分化调节中的作用提供了进一步的见解，这对骨修复具有重要意义。

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本文引用的文献

1
Current understanding on the molecular basis of chondrogenesis.关于软骨形成分子基础的当前认识。
Clin Pediatr Endocrinol. 2014 Jan;23(1):1-8. doi: 10.1292/cpe.23.1. Epub 2014 Feb 3.
2
miR-93/Sp7 function loop mediates osteoblast mineralization.miR-93/Sp7 功能循环介导成骨细胞矿化。
J Bone Miner Res. 2012 Jul;27(7):1598-606. doi: 10.1002/jbmr.1621.
3
MicroRNAs regulate osteogenesis and chondrogenesis.微小 RNA 调控成骨与软骨生成。
微小RNA在颌面部骨塑形和重塑中的作用：对错牙合畸形发生及正畸治疗的影响
Front Cell Dev Biol. 2024 Mar 13;12:1355312. doi: 10.3389/fcell.2024.1355312. eCollection 2024.
4
Single‑cell sequencing, genetics, and epigenetics reveal mesenchymal stem cell senescence in osteoarthritis (Review).单细胞测序、遗传学和表观遗传学揭示骨关节炎中间充质干细胞衰老（综述）。
Int J Mol Med. 2024 Jan;53(1). doi: 10.3892/ijmm.2023.5326. Epub 2023 Nov 8.
5
Effect of recombinant human fibroblast growth factor 21 on the mineralization of cementoblasts and its related mechanism.重组人成纤维细胞生长因子 21 对成牙骨质细胞矿化的影响及其相关机制。
Hua Xi Kou Qiang Yi Xue Za Zhi. 2023 Apr 1;41(2):140-148. doi: 10.7518/hxkq.2023.2022375.
6
Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review.miRNAs 和经典 TGF-β/BMP 信号通路在成骨细胞系中的转录后调控串扰：全面综述。
Int J Mol Sci. 2023 Mar 29;24(7):6423. doi: 10.3390/ijms24076423.
7
circRNA-ZCCHC14 affects the chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells by regulating GREM1 through miR-181a.circRNA-ZCCHC14 通过 miR-181a 调控 GREM1 影响外周血间充质干细胞的成软骨分化能力。
Sci Rep. 2023 Feb 18;13(1):2889. doi: 10.1038/s41598-023-29561-5.
8
miRNAs Related to Different Processes of Fracture Healing: An Integrative Overview.与骨折愈合不同过程相关的微小RNA：综合概述
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9
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Biochem Biophys Res Commun. 2012 Feb 24;418(4):587-91. doi: 10.1016/j.bbrc.2012.01.075. Epub 2012 Jan 27.
4
MicroRNA control of bone formation and homeostasis.微小 RNA 对骨形成和稳态的调控。
Nat Rev Endocrinol. 2012 Jan 31;8(4):212-27. doi: 10.1038/nrendo.2011.234.
5
The expression and function of microRNAs in chondrogenesis and osteoarthritis.微小RNA在软骨形成和骨关节炎中的表达及功能
Arthritis Rheum. 2012 Jun;64(6):1909-19. doi: 10.1002/art.34314. Epub 2011 Dec 5.
6
MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4.MicroRNA-146a 通过靶向 SMAD4 调节人真皮成纤维细胞中 TGF-β1 诱导的表型分化。
Arch Dermatol Res. 2012 Apr;304(3):195-202. doi: 10.1007/s00403-011-1178-0. Epub 2011 Oct 4.
7
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PLoS One. 2011;6(7):e21679. doi: 10.1371/journal.pone.0021679. Epub 2011 Jul 20.
8
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Eur Cell Mater. 2011 Jun 20;21:558-67. doi: 10.22203/ecm.v021a42.
9
MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo.MicroRNA-138 调控人基质（间质）干细胞的成骨分化。
Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6139-44. doi: 10.1073/pnas.1016758108. Epub 2011 Mar 28.
10
TGF-β regulates β-catenin signaling and osteoblast differentiation in human mesenchymal stem cells.TGF-β 调节人骨髓间充质干细胞中的 β-连环蛋白信号和成骨细胞分化。
J Cell Biochem. 2011 Jun;112(6):1651-60. doi: 10.1002/jcb.23079.