IR@PKUHSC  > 北京大学口腔医学院  > 口腔修复科
学科主题口腔医学
Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-kappa B
Yu, Bo1; Chang, Jia1; Liu, Yunsong2; Li, Jiong1; Kevork, Kareena1; Al-Hezaimi, Khalid3; Graves, Dana T.4; Park, No-Hee5,6; Wang, Cun-Yu1,7,8
刊名NATURE MEDICINE
2014-09-01
DOI10.1038/nm.3586
20期:9页:1009-1017
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology ; Medicine, Research & Experimental
资助者US National Institute of Dental and Craniofacial ; US National Institute of Arthritis and Musculoskeletal and Skin Diseases ; UCLA Broad Stem Cell Research Center Research Award ; US National Institute of Dental and Craniofacial ; US National Institute of Arthritis and Musculoskeletal and Skin Diseases ; UCLA Broad Stem Cell Research Center Research Award
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology ; Research & Experimental Medicine
关键词[WOS]MESENCHYMAL STEM-CELLS ; ACTIVATED PROTEIN-KINASE ; BONE LOSS ; OSTEOCLAST DEVELOPMENT ; POSTMENOPAUSAL WOMEN ; ESTROGEN DEFICIENCY ; BETA-CATENIN ; IN-VIVO ; OSTEOPOROSIS ; EXPRESSION
英文摘要

Aging-related bone loss and osteoporosis affect millions of people worldwide. Chronic inflammation associated with aging promotes bone resorption and impairs bone formation. Here we show that Wnt4 attenuates bone loss in osteoporosis and skeletal aging mouse models by inhibiting nuclear factor-kappa B (NF-kappa B) via noncanonical Wnt signaling. Transgenic mice expressing Wnt4 from osteoblasts were significantly protected from bone loss and chronic inflammation induced by ovariectomy, tumor necrosis factor or natural aging. In addition to promoting bone formation, Wnt4 inhibited osteoclast formation and bone resorption. Mechanistically, Wnt4 inhibited NF-kappa B activation mediated by transforming growth factor-beta-activated kinase-1 (Tak1) in macrophages and osteoclast precursors independently of beta-catenin. Moreover, recombinant Wnt4 alleviated bone loss and inflammation by inhibiting NF-kappa B in vivo in mouse models of bone disease. Given its dual role in promoting bone formation and inhibiting bone resorption, our results suggest that Wnt4 signaling could be an attractive therapeutic target for treating osteoporosis and preventing skeletal aging.

语种英语
所属项目编号DE19412 ; DE16513 ; AR63089
资助者US National Institute of Dental and Craniofacial ; US National Institute of Arthritis and Musculoskeletal and Skin Diseases ; UCLA Broad Stem Cell Research Center Research Award ; US National Institute of Dental and Craniofacial ; US National Institute of Arthritis and Musculoskeletal and Skin Diseases ; UCLA Broad Stem Cell Research Center Research Award
WOS记录号WOS:000341404000013
Citation statistics
Cited Times:59[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51028
Collection北京大学口腔医学院_口腔修复科
作者单位1.Univ Calif Los Angeles, Sch Dent, Lab Mol Signaling, Div Oral Biol & Med, Los Angeles, CA 90024 USA
2.Peking Univ, Dept Prosthodont, Sch & Hosp Stomatol, Beijing 100871, Peoples R China
3.King Saud Univ, Div Periodontol, Coll Dent, Engn AB Res Ctr Growth Factors & Bone Regenerat, Riyadh, Saudi Arabia
4.Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA
5.Univ Calif Los Angeles, Sch Dent, Div Diagnost & Surg Sci, Los Angeles, CA 90024 USA
6.Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA
7.Univ Calif Los Angeles, Broad Stem Cell Res Ctr, Los Angeles, CA USA
8.Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, Dept Bioengn, Los Angeles, CA USA
Recommended Citation
GB/T 7714
Yu, Bo,Chang, Jia,Liu, Yunsong,et al. Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-kappa B[J]. NATURE MEDICINE,2014,20(9):1009-1017.
APA Yu, Bo.,Chang, Jia.,Liu, Yunsong.,Li, Jiong.,Kevork, Kareena.,...&Wang, Cun-Yu.(2014).Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-kappa B.NATURE MEDICINE,20(9),1009-1017.
MLA Yu, Bo,et al."Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-kappa B".NATURE MEDICINE 20.9(2014):1009-1017.
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