Ameloblastin promotes bone growth by enhancing proliferation of progenitor cells and by stimulating immunoregulators
Ameloblastin promotes bone growth by enhancing proliferation of progenitor cells and by stimulating immunoregulators
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DOI：
10.1111/j.1600-0722.2010.00760.x
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发表时间：
2010-10-01
影响因子：
1.9
通讯作者：
Reseland, Janne E.
中科院分区：
文献类型：
--
作者：
Tamburstuen, Margareth V.;Reppe, Sjur;Reseland, Janne E.
在这项研究中，我们研究了釉基质蛋白成釉蛋白在骨生长和重塑中的作用，并试图确定这些过程中涉及的一些分子机制。重组成釉蛋白（rAmbn）的影响进行了测试，在大鼠体内，并在体外原代人间充质干细胞，成骨细胞，软骨细胞和破骨细胞。我们使用微阵列技术来鉴定人成骨细胞中受调控的基因，并使用多重蛋白质分析和实时RT-PCR来验证我们的发现。研究发现重组成釉蛋白在体内可以刺激骨愈合，在体外可以增强间充质干细胞和成骨细胞的增殖以及破骨细胞前体细胞的分化。最深刻的影响是对免疫应答相关基因的调节以及对细胞因子和骨细胞分化标志物的表达的影响，表明成釉蛋白对间充质细胞分化有影响。受体尚未确定，但我们发现rAmbn直接和间接诱导干扰素途径中的信号转导和转录激活因子（STAT）1和2以及下游因子。
In this study, we examined the role of the enamel matrix protein, ameloblastin, in bone growth and remodelling, and attempted to identify some of the molecular mechanisms involved in these processes. The effects of recombinant ameloblastin (rAmbn) were tested in vivo in rats, and in vitro in primary human mesenchymal stem cells, osteoblasts, chondrocytes, and osteoclasts. We used a microarray technique to identify genes that were regulated in human osteoblasts and verified our findings using multiplex protein analysis and real-time RT-PCR. Recombinant ameloblastin was found to stimulate bone healing in vivo, and to enhance the proliferation of mesenchymal stem cells and osteoblasts, as well as the differentiation of osteoclast precursor cells in vitro. The most profound effect was on the regulation of genes related to immune responses as well as on the expression of cytokines and markers of bone cell differentiation, indicating that ameloblastin has an effect on mesenchymal cell differentiation. A receptor has not yet been identified, but we found rAmbn to induce, directly and indirectly, signal transducer and activator of transcription (STAT) 1 and 2 and downstream factors in the interferon pathway.