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本文引用的文献

1
FGF-2 enhances Runx-2/Smads nuclear localization in BMP-2 canonical signaling in osteoblasts.成纤维细胞生长因子-2(FGF-2)增强骨形态发生蛋白-2(BMP-2)经典信号通路中 Runx-2/Smads 入核定位。
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2
Fibroblast growth factor-2 and bone morphogenetic protein-2 have a synergistic stimulatory effect on bone formation in cell cultures from elderly mouse and human bone.成纤维细胞生长因子-2 和骨形态发生蛋白-2 对老年鼠和人骨细胞培养物中的骨形成具有协同刺激作用。
J Gerontol A Biol Sci Med Sci. 2013 Oct;68(10):1170-80. doi: 10.1093/gerona/glt018. Epub 2013 Mar 26.
3
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4
FGF2-activated ERK mitogen-activated protein kinase enhances Runx2 acetylation and stabilization.成纤维细胞生长因子 2 激活的细胞外信号调节激酶丝裂原活化蛋白激酶增强 runt 相关转录因子 2 的乙酰化和稳定性。
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Nuclear isoforms of fibroblast growth factor 2 are novel inducers of hypophosphatemia via modulation of FGF23 and KLOTHO.成纤维细胞生长因子 2 的核异构体通过调节成纤维细胞生长因子 23 和 klotho 是低磷血症的新型诱导剂。
J Biol Chem. 2010 Jan 22;285(4):2834-46. doi: 10.1074/jbc.M109.030577. Epub 2009 Nov 20.
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Akt promotes BMP2-mediated osteoblast differentiation and bone development.Akt促进BMP2介导的成骨细胞分化和骨骼发育。
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Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1/2 and protein kinase C signaling.成纤维细胞生长因子受体2通过细胞外信号调节激酶1/2和蛋白激酶C信号通路促进间充质细胞的成骨分化。
J Biol Chem. 2009 Feb 20;284(8):4897-904. doi: 10.1074/jbc.M805432200. Epub 2008 Dec 30.
9
Endogenous FGF-2 is critically important in PTH anabolic effects on bone.内源性成纤维细胞生长因子-2在甲状旁腺激素对骨骼的合成代谢作用中至关重要。
J Cell Physiol. 2009 Apr;219(1):143-51. doi: 10.1002/jcp.21661.
10
Exported 18-kDa isoform of fibroblast growth factor-2 is a critical determinant of bone mass in mice.成纤维细胞生长因子2的18-kDa分泌型异构体是小鼠骨量的关键决定因素。
J Biol Chem. 2009 Jan 30;284(5):3170-3182. doi: 10.1074/jbc.M804900200. Epub 2008 Dec 4.

BMP-2 差异调节成骨细胞中 FGF-2 同工型的作用来自新生转基因小鼠。

BMP-2 differentially modulates FGF-2 isoform effects in osteoblasts from newborn transgenic mice.

机构信息

School of Biosciences and Biotechnology, University of Camerino, Camerino, MC, 62032 Italy.

出版信息

Endocrinology. 2013 Aug;154(8):2723-33. doi: 10.1210/en.2013-1025. Epub 2013 May 28.

DOI:10.1210/en.2013-1025
PMID:23715864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3713219/
Abstract

We previously generated separate lines of transgenic mice that specifically overexpress either the Fibroblast growth factor (FGF)-2 low-molecular-mass isoform (Tg(LMW)) or the high-mass isoforms (Tg(HMW)) in the osteoblast lineage. Vector/control (Tg(Vector)) mice were also made. Here we report the use of isolated calvarial osteoblasts (COBs) from those mice to investigate whether the FGF-2 protein isoforms differentially modulate bone formation in vitro. Our hypothesis states that FGF-2 isoforms specifically modulate bone morphogenetic protein 2 (BMP-2) function and subsequently bone differentiation genes and their related signaling pathways. We found a significant increase in alkaline phosphatase-positive colonies in Tg(LMW) COBs compared with Tg(Vector) controls. BMP-2 treatment significantly increased mineralized colonies in Tg(Vector) and Tg(LMW) COBs. BMP-2 caused a further significant increase in mineralized colonies in Tg(LMW) COBs compared with Tg(Vector) COBs but did not increase alkaline phosphatase-positive colonies in Tg(HMW) COBs. Time-course studies showed that BMP-2 caused a sustained increase in phosphorylated mothers against decapentaplegic-1/5/8 (Smad/1/5/8), runt-related transcription factor-2 (Runx-2), and osterix protein in Tg(LMW) COBs. BMP-2 caused a sustained increase in phospho-p38 MAPK in Tg(Vector) but only a transient increase in Tg(LMW) and Tg(HMW) COBs. BMP-2 caused a transient increase in phospho-p44/42 MAPK in Tg(Vector) COBs and no increase in Tg(LMW) COBs, but a sustained increase was found in Tg(HMW) COBs. Basal expression of FGF receptor 1 protein was significantly increased in Tg(LMW) COBs relative to Tg(Vector) COBs, and although BMP-2 caused a transient increase in FGF receptor 1 expression in Tg(Vector) COBs and Tg(HMW) COBs, there was no further increase Tg(LMW) COBs. Interestingly, although basal expression of FGF receptor 2 was similar in COBs from all genotypes, BMP-2 treatment caused a sustained increase in Tg(LMW) COBs but decreased FGF receptor 2 in Tg(Vector) COBs and Tg(HMW) COBs.

摘要

我们之前生成了分别在成骨细胞系中特异性过表达成纤维细胞生长因子 (FGF)-2 低分子量同种型 (Tg[LMW]) 或高分子量同种型 (Tg[HMW]) 的转基因小鼠系。还制作了载体/对照 (Tg[Vector]) 小鼠。在这里,我们报告使用来自这些小鼠的分离的颅盖骨成骨细胞 (COB) 来研究 FGF-2 蛋白同种型是否在体外差异调节骨形成。我们的假设是,FGF-2 同种型特异性调节骨形态发生蛋白 2 (BMP-2) 的功能,随后调节骨分化基因及其相关信号通路。我们发现 Tg[LMW] COB 中的碱性磷酸酶阳性集落数量明显增加,与 Tg[Vector]对照相比。BMP-2 处理显着增加了 Tg[Vector]和 Tg[LMW] COB 中的矿化集落。BMP-2 导致 Tg[LMW] COB 中的矿化集落进一步显着增加,与 Tg[Vector] COB 相比,但未增加 Tg[HMW] COB 中的碱性磷酸酶阳性集落。时程研究表明,BMP-2 导致 Tg[LMW] COB 中的磷酸化 mothers against decapentaplegic-1/5/8 (Smad/1/5/8)、 runt-related transcription factor-2 (Runx-2) 和 osterix 蛋白持续增加。BMP-2 导致 Tg[Vector]中的磷酸化 p38 MAPK 持续增加,但仅在 Tg[LMW]和 Tg[HMW] COB 中短暂增加。BMP-2 导致 Tg[Vector] COB 中的磷酸化 p44/42 MAPK 短暂增加,而 Tg[LMW] COB 无增加,但 Tg[HMW] COB 中发现持续增加。与 Tg[Vector] COB 相比,Tg[LMW] COB 中 FGF 受体 1 蛋白的基础表达显着增加,尽管 BMP-2 导致 Tg[Vector] COB 和 Tg[HMW] COB 中 FGF 受体 1 表达短暂增加,但 Tg[LMW] COB 没有进一步增加。有趣的是,尽管所有基因型 COB 中的 FGF 受体 2 基础表达相似,但 BMP-2 处理导致 Tg[LMW] COB 中的持续增加,而 Tg[Vector] COB 和 Tg[HMW] COB 中的 FGF 受体 2 减少。