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IR@PKUHSC  > 北京大学口腔医学院  > 第二门诊部  > 期刊论文
学科主题: 口腔医学
题名:
Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice
作者: Wu, Yuwei1,2,3; Tu, Qisheng1; Valverde, Paloma4; Zhang, Jin1; Murray, Dana1; Dong, Lily Q.5; Cheng, Jessica1; Jiang, Hua1; Rios, Maribel6; Morgan, Elise7,8,9; Tang, Zhihui2,3; Chen, Jake1,10,11
关键词: adiponectin ; hypothalamus ; adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif 1 ; bone marrow stromal cells ; tryptophan hydroxylase 2
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
发表日期: 2014-06-15
DOI: 10.1152/ajpendo.00048.2014
卷: 306, 期:12, 页:E1418-E1430
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism ; Physiology
研究领域[WOS]: Endocrinology & Metabolism ; Physiology
关键词[WOS]: SYMPATHETIC-NERVOUS-SYSTEM ; DOPAMINE-BETA-HYDROXYLASE ; PPAR-GAMMA ; INSULIN-RESISTANCE ; SUPPRESSING OSTEOCLAST ; HISTONE DEMETHYLASES ; LEPTIN REGULATION ; EXPRESSION ; DIFFERENTIATION ; HYPOTHALAMUS
英文摘要:

Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulinsensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C) expressions but decreased hypothalamic cannabinoid receptor-1 expression. Treatment of immortalized mouse neurons with APN demonstrated that APN-mediated effects on TPH2, CART, and Htr2C expression levels were abolished by downregulating adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL)-1 expression. Pharmacological increase in sympathetic activity stimulated adipogenic differentiation of bone marrow stromal cells (BMSC) and reversed APN-induced expression of the lysine-specific demethylases involved in regulating their commitment to the osteoblastic lineage. In conclusion, we found that APN regulates bone metabolism via central and peripheral mechanisms to decrease sympathetic tone, inhibit osteoclastic differentiation, and promote osteoblastic commitment of BMSC.

语种: 英语
所属项目编号: R01-DE-16710 ; R01-DE-21464 ; P30 NS047243
项目资助者: National Institute of Dental Research ; International Association for Dental Research and Academy of Osseointegration (Innovation in Implant Sciences) ; Tufts Center for Neuroscience Research
WOS记录号: WOS:000338418700008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57314
Appears in Collections:北京大学口腔医学院_第二门诊部_期刊论文

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作者单位: 1.Tufts Univ, Sch Dent Med, Div Oral Biol, Boston, MA 02111 USA
2.Wentworth Inst Technol, Dept Sci, Boston, MA USA
3.Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA
4.Boston Univ, Dept Mech Engn, Boston, MA 02215 USA
5.Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
6.Boston Univ, Dept Orthoped Surg, Boston, MA 02215 USA
7.Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA
8.Sackler Grad Sch Biomed Sci, Boston, MA USA
9.Peking Univ, Sch & Hosp Stomatol, Natl Engn Lab Digital & Mat Technol Stomatol, Beijing 100871, Peoples R China
10.Peking Univ, Sch & Hosp Stomatol, Dent Ctr 2, Beijing 100871, Peoples R China
11.Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA

Recommended Citation:
Wu, Yuwei,Tu, Qisheng,Valverde, Paloma,et al. Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice[J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM,2014,306(12):E1418-E1430.
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