MiR-29a是骨源性系统中矿物质沉积的增强剂

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Archives of biochemistry and biophysics Pub Date : 2014-12-15 DOI:10.1016/j.abb.2014.09.006
V.P. Roberto , D.M. Tiago , I.A.L. Silva , M.L. Cancela
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引用次数: 35

摘要

MicroRNAs (miRNAs)通过转录后调控为复杂的细胞过程提供了一种微调机制。新出现的证据表明,mirna在骨形成的调控中起关键作用。miR-29家族先前通过靶向细胞外基质分子和调节Wnt信号传导参与哺乳动物成骨细胞分化。然而,miR-29在骨形成和体内平衡中的功能尚不完全清楚。在这里,我们对miR-29a过表达在矿源细胞系统(ABSa15)中的生物学效应提供了新的见解。MiR-29a功能的获得导致细胞外基质矿化显著增加,可能是由于分化加速。我们还首次证明了miR-29a诱导β-catenin蛋白水平,这意味着对典型Wnt信号的刺激。我们的数据还表明,SPARC是miR-29a的保守靶点,可能有助于在ABSa15细胞中观察到的表型。最后,我们基于序列同源性、同步性分析和表达模式提供了miR-29a在进化过程中的保守性证据。综上所述,miR-29a是成骨分化的关键参与者,导致体外矿化增加,并且这种功能似乎通过与典型Wnt信号的相互作用和靶点的保护而在整个脊椎动物进化过程中保持不变。
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MiR-29a is an enhancer of mineral deposition in bone-derived systems

MicroRNAs (miRNAs) provide a mechanism for fine-tuning of intricate cellular processes through post-transcriptional regulation. Emerging evidences indicate that miRNAs play key roles in regulation of osteogenesis. The miR-29 family was previously implicated in mammalian osteoblast differentiation by targeting extracellular matrix molecules and modulating Wnt signaling. Nevertheless, the function of miR-29 in bone formation and homeostasis is not completely understood. Here, we provide novel insights into the biological effect of miR-29a overexpression in a mineralogenic cell system (ABSa15). MiR-29a gain-of-function resulted in significant increase of extracellular matrix mineralization, probably due to accelerated differentiation. We also demonstrated for the first time that miR-29a induced β-catenin protein levels, implying a stimulation of canonical Wnt signaling. Our data also suggests that SPARC is a conserved target of miR-29a, and may contribute to the phenotype observed in ABSa15 cells. Finally, we provide evidences for miR-29a conservation throughout evolution based on sequence homology, synteny analysis and expression patterns. Concluding, miR-29a is a key player in osteogenic differentiation, leading to increased mineralization in vitro, and this function seems to be conserved throughout vertebrate evolution by interaction with canonical Wnt signaling and conservation of targets.

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来源期刊
Archives of biochemistry and biophysics
Archives of biochemistry and biophysics 生物-生化与分子生物学
CiteScore
7.40
自引率
0.00%
发文量
245
审稿时长
26 days
期刊介绍: Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.
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