Wnt gene expression in the post-natal growth plate: Regulation with chondrocyte differentiation
Wnt gene expression in the post-natal growth plate: Regulation with chondrocyte differentiation
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DOI：
10.1016/j.bone.2007.01.005
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发表时间：
2007-05-01
期刊：
影响因子：
4.1
通讯作者：
Baron, Jeffrey
中科院分区：
文献类型：
--
作者：
Andrade, Anenisla C.;Nilsson, Ola;Baron, Jeffrey
长骨的纵向生长发生在生长板上，通过软骨内成骨。在胚胎小鼠中，这一过程受WRIT信号的调节。关于分泌信号蛋白WRIT家族中的哪些成员可能参与了对出生后生长板的调节，目前还知之甚少。我们利用显微切割和实时荧光定量聚合酶链式反应技术研究了WRIT基因在小鼠生长板中的表达。在已知的19个WRIT家族成员中，只有6个在出生后生长板中表达。其中，WRITS-2b、-4和-10b通过典型的β-连环蛋白途径传递信号，WRITS-5a、-5b和-11通过非典型的钙途径传递信号。这六个WRITS的空间表达非常相似，在试验区显示低表达，随着软骨细胞的增殖和前期肥大状态的分化而表达增加，然后随着软骨细胞的肥大分化而表达降低(Wnt-2b除外)。这一总体模式与先前对小鼠胚胎生长软骨的研究基本一致，表明WRIT信号调节软骨细胞的增殖和肥大分化。我们还发现，当纵向骨生长减弱时，这些WRIT基因的mRNA表达在4周时保持在相似的水平。综上所述，我们首次鉴定了在出生后哺乳动物生长板中表达的特定的WRIT基因。已鉴定的6个WRIT基因在软骨细胞分化过程中表现出相似的表达模式，提示在出生后软骨内骨形成中有重叠或相互作用的作用。(C)2007 Elsevier Inc.保留所有权利。
Longitudinal growth of long bones occurs at the growth plate by endochondral ossification. In the embryonic mouse, this process is regulated by Writ signaling. Little is known about which members of the Writ family of secreted signaling proteins might be involved in the regulation of the postnatal growth plate. We used microdissection and real-time PCR to study mRNA expression of Writ genes in the mouse growth plate. Of the 19 known members of the Writ family, only six were expressed in postnatal growth plate. Of these, Writs -2b, -4, and -10b signal through the canonical beta-catenin pathway and Writs -5a, -5b, and -11 signal through the noncanonical calcium pathway. The spatial expression for these six Writs was remarkably similar, showing low mRNA expression in the testing zone, increasing expression as the chondrocytes differentiated into the proliferative and prehypertrophic state and then (except Wnt-2b) decreasing expression as the chondrocytes underwent hypertrophic differentiation. This overall pattern is broadly consistent with previous studies of embryonic mouse growth cartilage Suggesting that Writ signaling modulates chondrocyte proliferation and hypertrophic differentiation. We also found that mRNA expression of these Writ genes persisted at similar levels at 4 weeks, when longitudinal bone growth is waning. In conclusion, we have identified for the first time the specific Writ genes that are expressed in the postnatal mammalian growth plate. The six identified Writ genes showed a similar pattern of expression during chondrocyte differentiation, suggesting overlapping or interacting roles in postnatal endochondral bone formation. (c) 2007 Elsevier Inc. All rights reserved.