2012年2月
Regulation of osteoblast differentiation by interleukin-11 via AP-1 and Smad signaling
ENDOCRINE JOURNAL
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- 巻
- 59
- 号
- 2
- 開始ページ
- 91
- 終了ページ
- 101
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1507/endocrj.EJ11-0219
- 出版者・発行元
- JAPAN ENDOCRINE SOC
Mechanical stress and parathyroid hormone (PTH) are major stimulators, and aging and glucocorticoids excess are important suppressors of osteoblast differentiation. Mechanical stress and PTH stimulate interleukin (IL)-11 expression in cells of osteoblast lineage by enhancing transcription of IL-11 gene via an increase in intracellular Ca2+. The elevated Ca2+ activates extracellular signal-regulated kinase (ERK) to enhance phosphorylation of cyclic AMP response element-binding protein (CREB), which binds to the fosB gene promoter and enhances Delta FosB expression. Delta FosB dimerizes with JunD on the IL-11 gene promoter to enhance its transcription. Both mechanical stress and PTH also stimulate phosphorylation of Smad1 via an activation of protein kinase C delta (PKC delta). Phosphorylated Smad1 binds to the IL-11 gene promoter and forms complex with Delta FosB/JunD to further enhance IL-11 gene transcription. The increased IL-11 then suppresses expression of Wnt inhibitors, including Dickkopf 1 (Dkk1) and 2, and enhances Wnt signaling to stimulate osteoblast differentiation and inhibit adipocyte differentiation. The suppression of osteoblast differentiation by aging involves a decrease in IL-11 gene transcription by a reduction in JunD binding to the activator protein (AP)-1 site of the IL-11 gene promoter. Glucocorticoids inhibit transcriptional activation of IL-11 gene by an interaction of glucocorticoid-glucocorticoid receptor (GR) complex with Delta FosB/JunD heterodimer. Thus, factors that enhance osteoblast differentiation stimulate, and those which suppress osteoblast differentiation inhibit IL-11 gene transcription, and IL-11 enhances Writ signaling by suppressing expression of its inhibitors. These observations are consistent with the notion that IL-11 mediates stimulatory and inhibitory signals of osteoblast differentiation by affecting Wnt signaling.
- リンク情報
- ID情報
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- DOI : 10.1507/endocrj.EJ11-0219
- ISSN : 0918-8959
- PubMed ID : 21931225
- Web of Science ID : WOS:000301962200001