Osteoactivin acts as downstream mediator of BMP-2 effects on osteoblast function
Osteoactivin acts as downstream mediator of BMP-2 effects on osteoblast function
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DOI：
10.1002/jcp.20841
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发表时间：
2007-01-01
影响因子：
5.6
通讯作者：
Safadi, Fayez F.
中科院分区：
文献类型：
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作者：
Abdelmagid, Samir M.;Barbe, Mary F.;Safadi, Fayez F.
我们的实验室之前表明，骨激活素（OA）是一种新型的、与成骨细胞相关的糖蛋白，在成骨细胞的分化和功能中发挥作用。本研究的目的是检查 BMP-2 对 OA 表达的调节以及 OA 作为 BMP-2 下游介质在成骨细胞功能中的作用。使用原代成骨细胞培养物，我们测试了不同剂量的BMP-2对成骨细胞发育过程中OA表达的调节。为了测试 Smad-1 信号传导是否负责 BMP-2 对 OA 表达的调节，用 Smad1 siRNA 转染成骨细胞培养物，用 50 ng/ml BMP-2 处理，并通过蛋白质印迹进行分析。 BMP-2 处理以剂量依赖性方式增加 OA mRNA 和蛋白质表达，并且这种上调在 Smad1 siRNA 转染的培养物中被阻断。接下来我们检查了 OA 作为 BMP-2 下游介质是否对成骨细胞分化和基质矿化产生影响。成骨细胞培养物用OA反义寡核苷酸转染并用50ng/ml的BMP-2处理。用OA反义寡核苷酸转染并用BMP-2处理的培养物显示出OA表达的减少，这与BMP-2诱导的早期和晚期分化标记物的显着减少相关。因此，OA 至少部分地充当 BMP-2 对成骨细胞分化和基质矿化作用的下游介质。我们的研究结果表明，BMP-2 通过 Smad1 信号通路调节 OA 表达。我们的数据还强调，OA 蛋白充当 BMP-2 对成骨细胞分化和功能影响的下游介质。
Our laboratory previously showed that osteoactivin (OA) is a novel, osteoblast-related glycoprotein that plays a role in osteoblast differentiation and function. The purpose of this study was to examine the regulation of OA expression by BMP-2 and the role OA plays as a downstream mediator of BMP-2 effects in osteoblast function. Using primary osteoblast cultures, we tested different doses of BMP-2 on the regulation of OA expression during osteoblast development. To test whether Smad-1 signaling is responsible for BMP-2 regulation of OA expression, osteoblast cultures were transfected with Smad1 siRNA, treated with 50 ng/ml of BMP-2 and analyzed by Western blot. BMP-2 treatment increased OA mRNA and protein expression in a dose-dependent manner and this upregulation was blocked in Smad1 siRNA transfected cultures. We next examined whether the role of OA as a downstream mediator of BMP-2 effects on osteoblast differentiation and matrix mineralization. Osteoblast cultures were transfected with OA antisense oligonucleotides and treated with 50 ng/ml of BMP-2. Cultures transfected with OA antisense oligonucleotides and treated with BMP-2 showed a reduction of OA expression associated with a significant reduction in early and late differentiation markers induced by BMP-2. Therefore, OA acts, at least in part, as a downstream mediator of BMP-2 effects on osteoblast differentiation and matrix mineralization. Our findings suggest that BMP-2 regulates OA expression through the Smad1 signaling pathway. Our data also emphasize that OA protein acts as a downstream mediator of BMP-2 effects on osteoblast differentiation and function.