Osteopontin is associated with nuclear factor κB gene expression during tail-suspension-induced bone loss
Osteopontin is associated with nuclear factor κB gene expression during tail-suspension-induced bone loss
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DOI：
10.1016/j.yexcr.2006.06.003
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发表时间：
2006-10-01
影响因子：
3.7
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
--
作者：
Ishijima, Muneaki;Ezura, Yoichi;Noda, Masaki
卸载所致的骨质疏松是现代老龄化社会的一个重要问题。虽然这种现象背后的机制在很大程度上尚不清楚，但骨桥蛋白(OPN)是卸载诱导的骨丢失所需的关键介质之一[M.Ishijima，S.R.Ritting，T.Yamashita，K.Tsuji，H.Kurosawa，A.Nifuji，D.T.Denhardt，and M.Noda，Enhmhance of Osteoclast bone Resorption and Inhibition Osteph细胞性bone Formation to Response of Osteopontin，J Exp Med，193(2001)399-404]。为了阐明OPN作用的分子基础，我们对野生型和OPN-/-小鼠的股骨骨髓细胞中表达的基因进行了微阵列分析。去掉机械负荷会导致野生型的骨丢失，但不会像以前报道的那样在OPN-/-小鼠中引起骨丢失。在基因芯片系统上对9586个基因的表达分析表明，OPN缺乏阻断了尾部悬吊诱导的10个基因的表达(A组)。基于半定量RT-PCR分析证实了这一观察结果。另一方面，4个基因(B组)的表达在野生型小鼠中未受尾部悬吊的影响，但在OPN缺陷小鼠中表达增强。尾部悬吊可上调野生型小鼠P53基因的表达，但在OPN-/-小鼠中不再表达。这些数据表明，OPN在编码凋亡相关分子的基因的上游介导机械应激信号，其作用与基因的改变有关。(C)2006 Elsevier Inc.保留所有权利。
Osteoporosis due to unloading-induced bone loss is a critical issue in the modem aging society. Although the mechanisms underlying this phenomenon are largely unknown, osteopontin (OPN) is one of the critical mediators required for unloading-induced bone loss [M. Ishijima, S.R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D.T. Denhardt, and M. Noda, Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin, J Exp Med, 193 (2001) 399-404]. To clarify the molecular bases for OPN actions, we carried out microarray analyses on the genes expressed in the femoral bone marrow cells in wild type and OPN-/- mice. The removal of the mechanical load induced bone loss in wild type, but not in OPN-/- mice, as previously reported. Expression analysis of 9586 cDNAs on a microarray system revealed that OPN deficiency blocked tail-suspension-induced expression of ten genes (group A). This observation was confirmed based on semi-quantitative RT-PCR analyses. On the other hand, expression of four genes (group B) was not altered by tail suspension in wild type but was enhanced in OPN-deficient mice. NF-kappa B p105 subunit gene (Nfkb1) was found in group A and Bax in group B. p53 gene expression was upregulated by tail suspension in wild type mice, but it was no longer observed in OPN-/- mice. These data indicate that OPN acts to mediate mechanical stress signaling upstream to the genes encoding apoptosis-related molecules, and its action is associated with alteration of the genes. (c) 2006 Elsevier Inc. All rights reserved.