Cell fusion in osteoclasts plays a critical role in controlling bone mass and osteoblastic activity

被引:52
作者
Iwasaki, Ryotaro [1 ,4 ]
Ninomiya, Ken [1 ,2 ]
Miyamoto, Kana [1 ,2 ]
Suzuki, Toru [1 ,2 ]
Sato, Yuiko [1 ,2 ,3 ]
Kawana, Hiromasa [4 ]
Nakagawa, Taneaki [4 ]
Suda, Toshio [1 ]
Miyamoto, Takeshi [1 ,2 ,3 ,5 ]
机构
[1] Keio Univ, Sch Med, Sakaguchi Lab Dev Biol, Dept Cell Differentiat,Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Dept Musculoskeletal Reconstruct & Regenerat Surg, Shinjuku Ku, Tokyo 1608582, Japan
[4] Keio Univ, Sch Med, Dept Dent & Oral Surg, Shinjuku Ku, Tokyo 1608582, Japan
[5] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan
基金
日本学术振兴会;
关键词
DC-STAMP; Osteoclast; Bone homeostasis; Transgenic; Cell-cell fusion; Uncoupling;
D O I
10.1016/j.bbrc.2008.10.076
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell-cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell-cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner. (C) 2008 Elsevier Inc. All rights reserved
引用
收藏
页码:899 / 904
页数:6
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