Endogenous FGF-2 is critically important in PTH anabolic effects on bone.
Endogenous FGF-2 is critically important in PTH anabolic effects on bone.
复制标题
内源性FGF-2在PTH合成代谢对骨骼的作用中至关重要。
DOI：
10.1002/jcp.21661
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发表时间：
2009-04
影响因子：
5.6
通讯作者：
Hurley, Marja M.
中科院分区：
文献类型：
--
作者：
Sabbieti, Maria Giovanna;Agas, Dimitrios;Xiao, Liping;Marchetti, Luigi;Coffin, J. Douglas;Doetschman, Thomas;Hurley, Marja M.
甲状旁腺激素可增加成骨细胞成纤维细胞生长因子受体-1和成纤维细胞生长因子-2的表达，−/−小鼠对甲状旁腺激素的合成反应降低。这项研究检测了在甲状旁腺激素的合成代谢反应中的候选因子是否在成骨细胞FGF2−/−中被调节。甲状旁腺激素可增加成纤维细胞生长因子2+/+的RUNX-2蛋白表达，但不增加成纤维细胞生长因子2−/−蛋白的表达。免疫细胞化学显示，PTH仅在FGF2+/+成骨细胞中诱导RUNX-2的核积聚。甲状旁腺素和成纤维细胞生长因子-2通过激活cAMP反应元件结合蛋白来调节RUNX-2。免疫印迹时程研究表明，甲状旁腺激素在15min内可使FGF2+/+细胞中磷酸化CREB的表达增强，并持续至24 h，而对FGF2−/−成骨细胞中的磷酸化CREB表达无影响。在FGF2+/+成骨细胞中沉默成纤维细胞生长因子-2可阻断甲状旁腺素对RUNX-2和CREBS磷酸化的刺激作用。甲状旁腺激素对成骨细胞前体增殖和凋亡相关蛋白的影响研究表明，甲状旁腺激素能增加成骨细胞−/−细胞周期蛋白D1CDK4/6的表达，但对成骨细胞周期蛋白D1CDK4/6的表达无影响。有趣的是，甲状旁腺素增加了成纤维细胞生长因子2−/−成骨细胞中细胞周期抑制因子p21/waf1的表达。甲状旁腺激素可增加成纤维细胞生长因子2+/+的Bcl2/bax蛋白比值，但不增加成纤维细胞生长因子2−/−的蛋白表达。此外，甲状旁腺激素可增加成纤维细胞生长因子2+/+的细胞存活率，但不能提高成纤维细胞生长因子2−/−的活性。提示内源性成纤维细胞生长因子-2在甲状旁腺激素对成骨细胞增殖、分化和凋亡的影响中起重要作用。这些因子的表达减少可能是FGF2−/−小鼠对甲状旁腺素的合成代谢反应减弱的原因之一。我们的结果有力地表明，合成代谢的甲状旁腺素效应部分依赖于成纤维细胞生长因子-2的表达。
Parathyroid hormone (PTH) increases Fibroblast growth factor receptor-1 (FGFR1) and Fibroblast growth factor-2 (FGF-2) expression in osteoblasts and the anabolic response to PTH is reduced in Fgf2−/− mice. This study examined whether candidate factors implicated in the anabolic response to PTH were modulated in Fgf2−/− osteoblasts. PTH increased Runx-2 protein expression in Fgf2+/+ but not Fgf2−/− osteoblasts. By immunocytochemistry, PTH treatment induced nuclear accumulation of Runx-2 only in Fgf2+/+ osteoblasts. PTH and FGF-2 regulate Runx-2 via activation of the cAMP response element binding proteins (CREBs). Western blot time course studies showed that PTH increased phospho-CREB within 15 min that was sustained for 24 h in Fgf2+/+ but had no effect in Fgf2−/− osteoblasts. Silencing of FGF-2 in Fgf2+/+ osteoblasts blocked the stimulatory effect of PTH on Runx-2 and CREBs phosphorylation. Studies of the effects of PTH on proteins involved in osteoblast precursor proliferation and apoptosis showed that PTH increased cyclinD1-cdk4/6 protein in Fgf2+/+ but not Fgf2−/− osteoblasts. Interestingly, PTH increased the cell cycle inhibitor p21/waf1 in Fgf2−/− osteoblasts. PTH increased Bcl-2/Bax protein ratio in Fgf2+/+ but not Fgf2−/− osteoblasts. In addition PTH increased cell viability in Fgf2+/+ but not Fgf2−/− osteoblasts. These data suggest that endogenous FGF-2 is important in PTH effects on osteoblast proliferation, differentiation and apoptosis. Reduced expression of these factors may contribute to the reduced anabolic response to PTH in the Fgf2−/− mice. Our results strongly indicate that the anabolic PTH effect is dependent in part on FGF-2 expression.
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影响因子：
2.5
作者：
Choi, KY;Kim, HJ;Ryoo, HM
通讯作者：
Ryoo, HM
影响因子：
15.9
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
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Manolagas, SC
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
4.7
作者：
Dong, M;Guda, K;Rosenberg, DW
通讯作者：
Rosenberg, DW
影响因子：
30.8
作者：
Knudson, CM;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ