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首页> 外文期刊>Cell and Tissue Research >Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1α
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Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1α

机译：Betacellulin通过HIF-1α抑制成骨细胞分化并刺激增殖

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摘要

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.
机译：通过表皮生长因子（EGF）和类EGF配体的细胞信号传导可以决定细胞命运和行为。成骨细胞负责形成和矿化类骨质，表达EGF受体并响应EGF受体激活而改变增殖和分化的速率。过表达EGF样配体βcellulin（BTC）的转基因小鼠表现出增加的皮质骨沉积。但是，由于转基因在这些小鼠中普遍表达，因此受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，我们检查了BTC对间充质干细胞（MSC）以及成骨细胞分化和增殖的影响。 BTC降低了MSC和成骨细胞中成骨标记的表达；有趣的是，由于HIF拮抗剂可阻止BTC驱动的增殖，因此增殖的增加需要缺氧诱导因子-α（HIF-α）。 MSC和成骨前细胞均表达EGF受体ErbB1，ErbB2和ErbB3，在成骨分化下其表达没有变化。这些是第一个证明BTC对MSC有影响的数据，也是第一个将HIF-α牵涉到BTC介导的增殖中的数据。

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