LMP-1, a LIM-domain protein, mediates BMP-6 effects on bone formation
LMP-1, a LIM-domain protein, mediates BMP-6 effects on bone formation
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DOI：
10.1210/en.139.12.5125
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发表时间：
1998-12-01
期刊：
影响因子：
4.8
通讯作者：
Titus, L
中科院分区：
文献类型：
--
作者：
Boden, SD;Liu, YS;Titus, L
糖皮质激素可促进胎儿颅骨细胞和骨髓基质细胞向成骨细胞分化。我们最近报道糖皮质激素特异性诱导骨形态发生蛋白-6（BMP-6），一种糖蛋白信号分子，是脊椎动物发育的多功能调节因子。在本研究中，我们使用胎鼠的第二次颅骨培养，以确定早期成骨细胞分化过程中诱导的基因，糖皮质激素，随后BMP-6，被发现诱导一种新的大鼠细胞内蛋白，LIM矿化蛋白-1（LMP-1），这反过来又导致合成一种或多种可溶性因子，可以诱导从头骨形成。用反义寡核苷酸阻断LMP-1的表达可阻止体外成骨细胞分化。使用哺乳动物表达载体过表达LMP-1足以在体外和体内皮下植入物中启动从头骨结节形成。这些数据表明，LMP-1是成骨细胞分化程序的重要正调节因子，也是BMP-6信号通路中的重要中间步骤。
Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow stromal cells. We recently reported that glucocorticoid specifically induced bone morphogenetic protein-6 (BMP-6), a glycoprotein signaling molecule that is a multifunctional regulator of vertebrate development. In the present study, we used fetal rat secondary calvarial cultures to determine genes induced during early osteoblast differentiation as initiated by glucocorticoid treatment.Glucocorticoid, and subsequently BMP-6, was found to induce a novel rat intracellular protein, LIM mineralization protein-1 (LMP-1), that in turn resulted in synthesis of one or more soluble factors that could induce de novo bone formation. Blocking expression of LMP-1 using antisense oligonucleotide prevented osteoblast differentiation in vitro. Overexpression of LMP-1 using a mammalian expression vector was sufficient to initiate de novo bone nodule formation in vitro and in sc implants in vivo. These data demonstrate that LMP-1 is an essential positive regulator of the osteoblast differentiation program as well as an important intermediate step in the BMP-6 signaling pathway.