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Overexpression of bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis.


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タイトル: Overexpression of bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis.
著者: Moriishi, Takeshi / Maruyama, Zenjiro / Fukuyama, Ryo / Ito, Masako / Miyazaki, Toshihiro / Kitaura, Hideki / Ohnishi, Hidetake / Furuichi, Tatsuya / Kawai, Yosuke / Masuyama, Ritsuko / Komori, Hisato / Takada, Kenji / Kawaguchi, Hiroshi / Komori, Toshihisa
発行日: 2011年11月17日
出版者: Public Library of Science
引用: PLoS One, 6(11), e27487; 2011
抄録: Bcl2 subfamily proteins, including Bcl2 and Bcl-X(L), inhibit apoptosis. As osteoblast apoptosis is in part responsible for osteoporosis in sex steroid deficiency, glucocorticoid excess, and aging, bone loss might be inhibited by the upregulation of Bcl2; however, the effects of Bcl2 overexpression on osteoblast differentiation and bone development and maintenance have not been fully investigated. To investigate these issues, we established two lines of osteoblast-specific BCL2 transgenic mice. In BCL2 transgenic mice, bone volume was increased at 6 weeks of age but not at 10 weeks of age compared with wild-type mice. The numbers of osteoblasts and osteocytes increased, but osteoid thickness and the bone formation rate were reduced in BCL2 transgenic mice with high expression at 10 weeks of age. The number of BrdU-positive cells was increased but that of TUNEL-positive cells was unaltered at 2 and 6 weeks of age. Osteoblast differentiation was inhibited, as shown by reduced Col1a1 and osteocalcin expression. Osteoblast differentiation of calvarial cells from BCL2 transgenic mice also fell in vitro. Overexpression of BCL2 in primary osteoblasts had no effect on osteoclastogenesis in co-culture with bone marrow cells. Unexpectedly, overexpression of BCL2 in osteoblasts eventually caused osteocyte apoptosis. Osteocytes, which had a reduced number of processes, gradually died with apoptotic structural alterations and the expression of apoptosis-related molecules, and dead osteocytes accumulated in cortical bone. These findings indicate that overexpression of BCL2 in osteoblasts inhibits osteoblast differentiation, reduces osteocyte processes, and causes osteocyte apoptosis.
URI: http://hdl.handle.net/10069/26842
ISSN: 19326203
DOI: 10.1371/journal.pone.0027487
PubMed ID: 22114675
権利: © 2011 Moriishi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:040 学術雑誌論文

引用URI : http://hdl.handle.net/10069/26842

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