Inhibition of osteoclast generation: a novel function of the bone morphogenetic protein 7/osteogenic protein 1.
Inhibition of osteoclast generation: a novel function of the bone morphogenetic protein 7/osteogenic protein 1.
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DOI：
10.1155/2012/171209
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发表时间：
2012
影响因子：
4.6
通讯作者：
Hänsch GM
中科院分区：
文献类型：
--
作者：
Maurer T;Zimmermann G;Maurer S;Stegmaier S;Wagner C;Hänsch GM
单核细胞具有向巨噬细胞、树突状细胞或破骨细胞分化的潜能。微环境，特别是细胞因子，引导单核细胞分化。核因子受体κB(RANK)配体、肿瘤坏死因子α或白介素8被认为是破骨细胞形成的诱导物，而其他如白介素10或转化生长因子则抑制破骨细胞的生成或诱导其向树突状细胞分化。我们现在描述骨形态发生蛋白(BMP)7/成骨蛋白-(OP-)1抑制人CD14+单核细胞向破骨细胞的分化。在BMP7/OP-1存在的情况下，转录因子c-Fos和NFATc1虽然在RANKL或IL-8的作用下上调并移位到细胞核，但并不持久。同时，单核细胞表达的转录因子MafB被保留下来，这是向巨噬细胞分化所必需的，但它抑制了破骨细胞的生成。由于NFATc1的持续存在和MafB的下调对破骨细胞的形成都是至关重要的，我们得出结论，BMP7/OP-1通过干扰信号通路来抑制破骨细胞的产生。
Monocytes have the potential to differentiate to either macrophages, dendritic cells, or to osteoclasts. The microenvironment, particularly cytokines, directs the monocyte differentiation. Receptors of NFκB (RANK) ligand, tumor necrosis factor (TNF) α, or interleukin- (IL-) 8 have be identified as inducers of osteoclastogenesis, whereas others, such as IL-10 or transforming growth factor (TGF)ß inhibit osteoclast generation or induce differentiation towards a dendritic cell type. We now describe that bone morphogenetic protein (BMP) 7/osteogenic protein- (OP-) 1 inhibited the differentiation of human CD14+ monocytes to osteoclasts. In the presence of BMP7/OP-1 the transcription factors c-Fos and NFATc1, though upregulated and translocated to the nucleus in response to either RANKL or IL-8, did not persist. In parallel, MafB, a transcription factor expressed by monocytes and required for differentiation to macrophages but inhibiting osteoclast generation, was preserved. Because both persistence of NFATc1 and downregulation of MafB are crucial for osteoclastogenesis, we conclude that BMP7/OP-1 inhibits the generation of osteoclasts by interfering with signalling pathways.
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影响因子：
3.7
作者：
Perron JC;Dodd J
通讯作者：
Dodd J
影响因子：
15.3
作者：
Asagiri, M;Sato, K;Takayanagi, H
通讯作者：
Takayanagi, H
DOI：
10.1073/pnas.85.15.5683
发表时间：
1988-08-01
影响因子：
11.1
作者：
CHENU, C;PFEILSCHIFTER, J;ROODMAN, GD
通讯作者：
ROODMAN, GD
影响因子：
20.3
作者：
Kim, Kabsun;Kim, Jung Ha;Kim, Nacksung
通讯作者：
Kim, Nacksung
DOI：
10.1016/s0020-1383(08)70017-2
发表时间：
2008-09-01
影响因子：
2.5
作者：
Donati, D.;Di Bella, C.;Giardino, R.
通讯作者：
Giardino, R.