Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1alpha.
Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1alpha.
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DOI：
10.1007/s00441-010-0929-0
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发表时间：
2010-04
影响因子：
3.6
通讯作者：
Vidal, Martin A.
中科院分区：
文献类型：
--
作者：
Genetos, Damian C.;Rao, Rameshwar R.;Vidal, Martin A.
通过表皮生长因子（EGF）和EGF样配体的细胞信号传导可以决定细胞的命运和行为。成骨细胞负责形成和矿化类骨质，表达EGF受体，并响应EGF受体活化而改变增殖和分化速率。过表达EGF样配体β细胞素（BTC）的转基因小鼠表现出皮质骨沉积增加;然而，由于转基因在这些小鼠中普遍表达，受BTC影响并导致皮质骨厚度增加的细胞的身份仍然未知。因此，我们研究了BTC对间充质干细胞（MSC）和前成骨细胞分化和增殖的影响。BTC降低了MSC和成骨细胞前体中成骨标志物的表达;有趣的是，增殖的增加需要缺氧诱导因子-α（HIF-α），因为HIF拮抗剂可以阻止BTC驱动的增殖。MSC和前成骨细胞均表达EGF受体ErbB 1、ErbB 2和ErbB 3，在成骨分化下表达无变化。这些是证明BTC对MSC的影响的第一个数据，也是第一个表明HIF-α参与BTC介导的增殖的数据。
Cellular signaling via epidermal growth factor (EGF) and EGF-like ligands can determine cell fate and behavior. Osteoblasts, which are responsible for forming and mineralizing osteoid, express EGF receptors and alter rates of proliferation and differentiation in response to EGF receptor activation. Transgenic mice over-expressing the EGF-like ligand betacellulin (BTC) exhibit increased cortical bone deposition; however, because the transgene is ubiquitously expressed in these mice, the identity of cells affected by BTC and responsible for increased cortical bone thickness remains unknown. We have therefore examined the influence of BTC upon mesenchymal stem cell (MSC) and pre-osteoblast differentiation and proliferation. BTC decreases the expression of osteogenic markers in both MSCs and pre-osteoblasts; interestingly, increases in proliferation require hypoxia-inducible factor-alpha (HIF-α), as an HIF antagonist prevents BTC-driven proliferation. Both MSCs and pre-osteoblasts express EGF receptors ErbB1, ErbB2, and ErbB3, with no change in expression under osteogenic differentiation. These are the first data that demonstrate an influence of BTC upon MSCs and the first to implicate HIF-α in BTC-mediated proliferation.
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影响因子：
9.7
作者：
Chun, YS;Yeo, EJ;Park, JW
通讯作者：
Park, JW
影响因子：
4.8
作者：
Chan, SY;Wong, RWC
通讯作者：
Wong, RWC
DOI：
10.1016/0169-6009(90)90117-x
发表时间：
1990-02-01
期刊：
BONE AND MINERAL
影响因子：
--
作者：
NICOLAS, V;NEFUSSI, JR;FOREST, N
通讯作者：
FOREST, N
DOI：
10.1016/j.bbrc.2008.09.145
发表时间：
2008-12-12
影响因子：
3.1
作者：
Pacary, Emilie;Petit, Edwige;Bernaudin, Myriam
通讯作者：
Bernaudin, Myriam
影响因子：
5.6
作者：
Kanichai, Manoj;Ferguson, Damien;Campbell, Veronica A.
通讯作者：
Campbell, Veronica A.