Spaciotemporal association and bone morphogenetic protein regulation of Sclerostin and Osterix expression during embryonic osteogenesis
Spaciotemporal association and bone morphogenetic protein regulation of Sclerostin and Osterix expression during embryonic osteogenesis
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DOI：
10.1210/en.2003-1492
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发表时间：
2004-10-01
期刊：
影响因子：
4.8
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Ohyama, Y;Nifuji, A;Noda, M
硬化蛋白（SOST）是胱氨酸结超家族的一员，对正常的骨骼发生至关重要，因为SOST基因的功能缺失突变导致人类以大量骨生长为特征的硬化性骨形成。为了了解SOST在发育骨骼组织形成中的功能，我们检测了SOST基因在体外和体内胚胎成骨中的表达。在原代颅骨细胞成骨细胞分化过程中，SOST的表达水平随着碱性磷酸酶活性和结节形成的水平沿着增加。原位杂交结果显示，SOST mRNA在胚胎13 d的肢芽中表达于趾部，在胚胎交配后16.5 d的颅骨中表达于成骨前缘，在胚胎交配后18.5 d的颅骨中仍有表达。这些在体内和体外的时空表达模式是平行的osterix（Osx），这是一个关键的骨形成转录因子。在骨形态发生蛋白（BMP）2存在下体外培养的原代成骨细胞中，观察到类似的SOST和Osx mRNA的共表达。此外，内源性表达的SOST和Osx mRNA被抑制的noggin表达腺病毒感染到原代成骨细胞颅骨细胞，这表明内源性骨形成蛋白是这些细胞表达SOST和Osx mRNA所必需的。因此，SOST在BMP调控下的表达和调节与Osx在体内和体外的表达和调节密切相关。
Sclerostin (SOST), a member of the cystine-knot superfamily, is essential for proper skeletogenesis because a loss-of-function mutation in the SOST gene results in sclerosteosis featured with massive bone growth in humans. To understand the function of SOST in developmental skeletal tissue formation, we examined SOST gene expression in embryonic osteogenesis in vitro and in vivo. During osteoblastic differentiation in primary calvarial cells, the levels of SOST expression were increased along with those of alkaline phosphatase activity and nodule formation. In situ hybridization study revealed that SOST mRNA expression was observed in the digits in embryonic 13-d limb buds, and SOST expression was observed in osteogenic front in embryonic 16.5-d postcoitus embryonic calvariae, and this expression persisted in the peripheral area of cranial bone in the later developmental stage (embryonic 18.5-d post coitum). These temporal and spacial expression patterns in vivo and in vitro were in parallel to those of osterix (Osx), which is a critical transcriptional factor for bone formation. Similar coexpression of SOST and Osx mRNA was observed when the primary osteoblastic calvarial cells were cultured in the presence of bone morphogenetic protein (BMP)2 in vitro. Moreover, endogenous expression of SOST and Osx mRNA was inhibited by infection of noggin-expression adenovirus into the primary osteoblastic calvarial cells, suggesting that endogenous BMPs are required for these cells to express SOST and Osx mRNA. Thus, expression and regulation of SOST under the control of BMP were closely associated with those of Osx in vivo and in vitro.