求助几篇文章

clairezy1983

Expert Opin Ther Targets. 2011 May;15(5):623-36. Epub 2011 Feb 28.
0 ^, {/ K" L" |- F; LMicroRNAs in adipogenesis and as therapeutic targets for obesity.! U3 O# O. r$ I. h6 W! D, P
Alexander R, Lodish H, Sun L.4 T+ }+ ]1 O  u& Q$ I
SourceWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA sun@wi.mit.edu.
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Abstract. f" `4 k* T4 F' i- {8 R
Introduction: Obesity and obesity-related disease have reached pandemic proportions and are prevalent even in developing countries. Adipose tissue is increasingly being recognized as a key regulator of whole-body energy homeostasis and consequently as a prime therapeutic target for metabolic syndrome. This review discusses the roles of miRNAs, small endogenously expressed RNAs that regulate gene expression at a post-transcriptional level, in the development and function of adipose tissue and other relevant metabolic tissues impacted by obesity. Several high-throughput studies have identified hundreds of miRNAs that are differentially expressed during the development of metabolic tissues or as an indication of pathophysiology. Further investigation has functionalized the regulatory capacity of individual miRNAs and revealed putative targets for these miRNAs. Therefore, as with several other pathologies, miRNAs are emerging as feasible therapeutic targets for metabolic syndrome. Areas covered: This review provides a comprehensive view of miRNAs involved in adipogenesis, from mesenchymal stem cell lineage determination through terminal adipocyte differentiation. We also discuss the differential expression of miRNAs among adipose depots and the dysregulation of miRNAs in other metabolic tissues during metabolic pathophysiology. Finally, we discuss the therapeutic potential of targeting miRNAs in obesity and give a perspective on the challenges and advantages of miRNA-based drugs. Expert opinion: miRNAs are extensive regulators of adipocyte development and function and are viable therapeutic targets for obesity. Despite the broad-spectrum and redundancy of miRNA-target interactions, sophisticated bioinformatic approaches are making it possible to determine the most physiologically relevant miRNAs to target in disease. In vivo delivery of miRNAs for therapeutic purposes is rapidly developing and has been successful in other contexts. Additionally, miRNAs can be used as prognosis markers for disease onset and progression. Ultimately, miRNAs are prime therapeutic targets for obesity and its consequent pathologies in other metabolic tissues.  H; X$ w; T) k# R7 H
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PMID: 21355787 [PubMed - in process]

clairezy1983

求助求助
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Blood. 2011 Mar 31;117(13):3648-57. Epub 2011 Jan 27.
) k' D6 s  [/ M. q1 {A microRNA expression signature of osteoclastogenesis.- K& B3 O. `$ t' \# t# i
Sugatani T, Vacher J, Hruska KA.
0 T& t9 J+ @6 ISourceDepartment of Pediatrics, Washington University School of Medicine, St Louis, MO; and./ p# y1 |: X# ?  J. @' |% \
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Abstract
+ ]' y) {  T" i& ?9 x$ h9 ~/ g- X3 xMicroRNAs (miRs) are small noncoding RNAs that principally function in the spatiotemporal regulation of protein translation in animal cells. Although emerging evidence suggests that some miRs play important roles in osteoblastogenesis and skeletal homeostasis, much less is known in osteoclastogenesis. Here, we show that receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis is mediated by miR-21. MiR-21 was identified as an miR expression signature of RANKL-induced osteoclastogenesis that down-regulates programmed cell death 4 (PDCD4) protein levels. Diminished PDCD4 removes a repression from c-Fos, a critical transcription factor for osteoclastogenesis and osteoclast-specific downstream target genes. In addition, RANKL-induced c-Fos up-regulates miR-21 gene expression. Bone marrow-derived monocyte/macrophage precursors deficient of DiGeorge syndrome critical region gene 8, an RNA binding protein associated with miR biogenesis, and Dicer, an endoribonuclease in the RNaseIII family associated with miR biogenesis, possessed significantly decreased miR-21 levels and increased PDCD4 protein levels so that RANKL-induced osteoclastogenesis was impaired in those cells. However, forced expression of miR-21 rescued osteoclast development because of down-regulation of PDCD4 protein expression levels. Thus, our studies provide a new molecular mechanism, including a positive feedback loop of c-Fos/miR-21/PDCD4, regulating osteoclastogenesis.
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3 U* Y: u0 ~1 t, zPMID: 21273303 [PubMed - in process] PMCID: PMC3072882[Available on 2012/3/31]

clairezy1983

Expert Opin Ther Targets. 2010 Oct;14(10):1109-20.. R0 ]' D6 B5 N& d3 A5 Y, M( U
Targeting miRNAs in osteoblast differentiation and bone formation.$ I: M6 o3 \3 d0 K- z/ {& P
Hu R, Li H, Liu W, Yang L, Tan YF, Luo XH.) j: c( K! j4 }: v( a& c
SourceThe Second Xiangya Hospital of Central South University, Institute of Endocrinology & Metabolism, Changsha, Hunan 410011, PR China.; F5 p& R- K- K
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Abstract/ ~2 t. y, o. F" I' b* f
IMPORTANCE OF THE FIELD: Bone tissue arises from mesenchymal stromal cells (MSCs) differentiated into the osteoblast lineage by genetic and epigenetic mechanisms. Emerging evidence indicates that the class of small non-coding single-stranded RNAs known as "microRNAs (miRNAs)" also plays a critical role in this process.8 ]4 c6 U! U& Y! h

& {, a0 n( K- G9 K1 UAREAS COVERED IN THIS REVIEW: In this short review, we summarize the biology and functional mechanisms of miRNAs. Importantly, we discuss miRNA expression, miRNA function, miRNA target prediction, miRNA overexpression and inhibition methods applied in osteoblastogenesis.
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+ c0 a" ~" Q% Q  b* s( lWHAT THE READER WILL GAIN: We discuss the potential therapeutic opportunities and challenges for improving the treatment of bone-related diseases by using miRNAs as a therapeutic target.
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TAKE HOME MESSAGE: Although various microRNAs regulate cell proliferation and differentiation, only a few miRNAs has been reported so far to play a key role in the regulation of osteoblast differentiation and bone formation.4 L' e  e' t7 Q0 C

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ceming

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clairezy1983

感谢感谢啊

clairezy1983

回复 ceming 的帖子
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+ J- R- V  O; m0 a$ z5 i7 R. a谢谢你了，ceming