共 33 条
The murine glucagon-like peptide-1 receptor is essential for control of bone resorption
被引:241
作者:
Yamada, Chizumi
[2
]
Yamada, Yuichiro
[1
,2
]
Tsukiyama, Katsushi
[2
,6
]
Yamada, Kotaro
[2
]
Udagawa, Nobuyuki
[4
]
Takahashi, Naoyuki
[5
]
Tanaka, Kiyoshi
Drucker, Daniel J.
[7
,8
]
Seino, Yutaka
[2
,9
]
Inagaki, Nobuya
[2
,3
]
机构:
[1] Akita Univ, Sch Med, Dept Internal Med, Div Endocrinol Diabet & Geriatr Med, Akita 0108543, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Diabet & Clin Nutr, Kyoto 6068507, Japan
[3] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Kyoto 6068507, Japan
[4] Matsumoto Dent Univ, Dept Biochem, Nagano 3990781, Japan
[5] Matsumoto Dent Univ, Inst Oral Sci, Nagano 3990781, Japan
[6] Kyoto Womens Univ, Dept Nutr, Kyoto 6058501, Japan
[7] Univ Toronto, Samuel Lunenfeld Res Inst, Dept Med, Mt Sinai Hosp, Toronto, ON M5G 2C4, Canada
[8] Univ Toronto, Bating & Best Diabet Ctr, Toronto, ON M5G 2C4, Canada
[9] Kansai Elect Power Hosp, Osaka 5530003, Japan
关键词:
D O I:
10.1210/en.2007-1292
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Gastrointestinal hormones including gastric inhibitory polypeptide ( GIP), glucagon-like peptide (GLP)-1, and GLP-2 are secreted immediately after meal ingestion, and GIP and GLP-2 have been shown to regulate bone turnover. We hypothesize that endogenous GLP-1 may also be important for control of skeletal homeostasis. We investigated the role of GLP-1 in the regulation of bone metabolism using GLP-1 receptor knockout (Glp-1r(-/-)) mice. A combination of bone density and histomorphometry, osteoclast activation studies, biochemical analysis of calcium and PTH, and RNA analysis was used to characterize bone and mineral homeostasis in Glp1r(-/-) and Glp-1r(-/-) littermate controls. Glp-1r(-)/(-) mice have cortical osteopenia and bone fragility by bone densitometry as well as increased osteoclastic numbers and bone resorption activity by bone histomorphometry. Although GLP-1 had no direct effect on osteoclasts and osteoblasts, Glp-1r(-/-) mice exhibited higher levels of urinary deoxypyridinoline, a marker of bone resorption, and reduced levels of calcitonin mRNA transcripts in the thyroid. Moreover, calcitonin treatment effectively suppressed urinary levels of deoxypyridinoline in Glp-1r(-/-), mice and the GLP-1 receptor agonist exendin-4 increased calcitonin gene expression in the thyroid of wild-type mice. These findings establish an essential role for endogenous GLP-1 receptor signaling in the control of bone resorption, likely through a calcitonin-dependent pathway.
引用
收藏
页码:574 / 579
页数:6
相关论文