Varley J E, Wehby R G, Rueger D C, Maxwell G D
Neuroscience Program, University of Connecticut Health Center, Farmington 06030-3405, USA.
Dev Dyn. 1995 Aug;203(4):434-47. doi: 10.1002/aja.1002030406.
OP-1, also known as BMP-7, is a member of the TGF-beta superfamily of proteins and was originally identified on the basis of its ability to induce new bone formation in vivo. OP-1 mRNA is found in the developing kidney and adrenal gland as well as in some brain regions (Ozkaynak et al. [1991] Biochem. Biophys. Res. Commun. 179:116-123). We have tested the effect of recombinant human OP-1 on quail trunk neural crest cultures. The number of catecholamine-positive cells which developed after 7 days in vitro in the presence of OP-1 was increased in a dose-dependent manner, with a greater than 100-fold maximal stimulation observed. The increase in the number of catecholamine-positive cells in the presence of OP-1 was paralleled by an increase in the number of tyrosine hydroxylase (TH)-positive cells. In contrast, total and melanocyte cell number were unaffected by the presence of OP-1. The number of Islet-1-immunoreactive cells was also increased by OP-1, but to only about half the value seen for TH. Double label experiments revealed these Islet-1-positive cells were a subset of the TH-positive cells. Inhibitors of DNA synthesis prevented the OP-1-mediated increase in adrenergic cell number, indicating that OP-1 does not act on a postmitotic cell population. However, labeling studies with bromodeoxyuridine indicated that OP-1 did not increase the proportion of the cell population engaged in DNA synthesis. Thus, the OP-1-mediated increase in adrenergic cell number most likely occurs as a result of the enhanced survival of a subpopulation of adrenergic precursors or an increase in their probability of adrenergic differentiation, but not by increasing the mitotic rate of adrenergic precursors or adrenergic cells themselves. In contrast to OP-1, TGF-beta 1 decreased adrenergic cell number. When OP-1 and TGF-beta 1 were added simultaneously, TGF-beta 1 antagonized the OP-1-mediated increase in adrenergic cell number in a dose-dependent manner.
OP-1，也被称为骨形态发生蛋白-7（BMP-7），是转化生长因子-β（TGF-β）超家族蛋白的成员，最初是根据其在体内诱导新骨形成的能力而被鉴定出来的。OP-1信使核糖核酸（mRNA）在发育中的肾脏、肾上腺以及一些脑区中被发现（奥兹凯纳克等人[1991年]《生物化学与生物物理研究通讯》179:116 - 123）。我们已经测试了重组人OP-1对鹌鹑躯干神经嵴培养物的影响。在体外培养7天后，在OP-1存在的情况下发育出的儿茶酚胺阳性细胞数量呈剂量依赖性增加，观察到最大刺激超过100倍。在OP-1存在的情况下，儿茶酚胺阳性细胞数量的增加与酪氨酸羟化酶（TH）阳性细胞数量的增加平行。相比之下，总细胞数和黑素细胞数不受OP-1存在的影响。胰岛-1免疫反应性细胞的数量也因OP-1而增加，但仅约为TH所见值的一半。双重标记实验表明，这些胰岛-1阳性细胞是TH阳性细胞的一个子集。DNA合成抑制剂阻止了OP-1介导的肾上腺素能细胞数量增加，表明OP-1并不作用于有丝分裂后细胞群体。然而，用溴脱氧尿苷进行的标记研究表明，OP-1并没有增加参与DNA合成的细胞群体比例。因此，OP-1介导的肾上腺素能细胞数量增加最有可能是由于肾上腺素能前体细胞亚群的存活率提高或其肾上腺素能分化概率增加，而不是通过增加肾上腺素能前体细胞或肾上腺素能细胞本身的有丝分裂率。与OP-1相反，TGF-β1减少了肾上腺素能细胞数量。当同时添加OP-1和TGF-β1时，TGF-β1以剂量依赖性方式拮抗OP-1介导的肾上腺素能细胞数量增加。
