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学科主题: 口腔医学
题名:
MSC Transplantation Improves Osteopenia via Epigenetic Regulation of Notch Signaling in Lupus
作者: Liu, Shiyu1,2,3; Liu, Dawei1,3,4; Chen, Chider1,3; Hamamura, Kazunori3; Moshaverinia, Alireza3; Yang, Ruili1,3,4; Liu, Yao3; Jin, Yan2; Shi, Songtao1,3
刊名: CELL METABOLISM
发表日期: 2015-10-06
DOI: 10.1016/j.cmet.2015.08.018
卷: 22, 期:4, 页:606-618
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Endocrinology & Metabolism
研究领域[WOS]: Cell Biology ; Endocrinology & Metabolism
关键词[WOS]: MESENCHYMAL STEM-CELLS ; DNA METHYLTRANSFERASE 1 ; VERSUS-HOST-DISEASE ; STROMAL CELLS ; OSTEOBLAST DIFFERENTIATION ; HYPOMETHYLATION ; ERYTHEMATOSUS ; EXOSOMES ; MACROPHAGES ; MECHANISMS
英文摘要:

Mesenchymal stem cell transplantation (MSCT) has been used to treat human diseases, but the detailed mechanisms underlying its success are not fully understood. Here we show that MSCT rescues bone marrow MSC (BMMSC) function and ameliorates osteopenia in Fas-deficient-MRL/lpr mice. Mechanistically, we show that Fas deficiency causes failure of miR-29b release, thereby elevating intracellular miR-29b levels, and downregulates DNA methyltransferase 1 (Dnmt1) expression in MRL/lpr BMMSCs. This results in hypomethylation of the Notch1 promoter and activation of Notch signaling, in turn leading to impaired osteogenic differentiation. Furthermore, we show that exosomes, secreted due to MSCT, transfer Fas to recipient MRL/lpr BMMSCs to reduce intracellular levels of miR-29b, which results in recovery of Dnmt1-mediated Notch1 promoter hypomethylation and thereby improves MRL/lpr BMMSC function. Collectively our findings unravel the means by which MSCT rescues MRL/lpr BMMSC function through reuse of donor exosome-provided Fas to regulate the miR-29b/Dnmt1/Notch epigenetic cascade.

语种: 英语
所属项目编号: R01DE017449 ; R01DE019932 ; 81020108019 ; 2011CB964700
项目资助者: National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services ; National Natural Science Foundation of China ; National Basic Research Program (973 Program) of China
WOS记录号: WOS:000365192600011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53650
Appears in Collections:北京大学口腔医学院_牙周科_期刊论文

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作者单位: 1.Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA
2.Fourth Mil Med Univ, Sch Stomatol, Ctr Tissue Engn, State Key Lab Mil Stomatol, Xian 710032, Shaanxi, Peoples R China
3.Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA
4.Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China

Recommended Citation:
Liu, Shiyu,Liu, Dawei,Chen, Chider,et al. MSC Transplantation Improves Osteopenia via Epigenetic Regulation of Notch Signaling in Lupus[J]. CELL METABOLISM,2015,22(4):606-618.
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