Andrews P W, Damjanov I, Berends J, Kumpf S, Zappavigna V, Mavilio F, Sampath K
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.
Lab Invest. 1994 Aug;71(2):243-51.
Osteogenic protein-1 (OP-1) is a member of the transforming growth factor-beta super family closely related to the bone morphogenetic proteins and also known as bone morphogenetic protein-7. Other members of this family of growth factors influence cell differentiation as well as cell growth in a number of systems. The Drosophila homolog encoded by the decapentaplegic locus is involved in dorsal-ventral pattern formation during embryogenesis, whereas the expression of several bone morphogenetic proteins including OP-1 is developmentally regulated in mammalian embryos.
The effect of recombinant human OP-1 on the proliferation and differentiation of an established pluripotent human embryonal carcinoma (EC) cell line, NTERA2, and three nullipotent human EC cell lines, 2102Ep, 833KE and TERA-1, was investigated. These cells were grown under reduced serum conditions, and differentiation was monitored by morphology and expression of marker antigens.
OP-1 inhibited proliferation of NTERA2 and induced their differentiation, marked by changes in cellular morphology, the loss of EC cell antigens (SSEA3, SSEA4, the liver isozyme of alkaline phosphatase), and the appearance of new antigens, notably SSEA1 and class 1 major histocompatibility complex antigens. These changes were irreversible and did not involve significant cell degeneration or cell death. The OP-1-induced differentiation of NTERA2 appeared distinct from that induced by either retinoic acid or hexamethylene bisacetamide. Nevertheless, OP-1 did induce the homeobox gene, HOXA1. By contrast, OP-1 elicited only a limited and partial response from the nullipotent EC cell lines.
Our results suggest that pluripotent human EC cells differentiate in response to OP-1 and that this factor can modulate the differentiation induced by retinoic acid. Like other members of the transforming growth factor-beta super family, OP-1 might play an inductive role in the early embryo. The results also suggest a possible therapeutic value for OP-1 in the treatment of some germ cell tumors.
成骨蛋白-1（OP-1）是转化生长因子-β超家族的成员，与骨形态发生蛋白密切相关，也被称为骨形态发生蛋白-7。该生长因子家族的其他成员在许多系统中影响细胞分化以及细胞生长。由果蝇的“截瘫”基因座编码的同源物参与胚胎发育过程中的背腹模式形成，而包括OP-1在内的几种骨形态发生蛋白的表达在哺乳动物胚胎中受到发育调控。
研究了重组人OP-1对已建立的多能性人胚胎癌细胞系NTERA2以及三种无潜能性人胚胎癌细胞系2102Ep、833KE和TERA-1增殖和分化的影响。这些细胞在低血清条件下培养，并通过形态学和标记抗原的表达监测分化情况。
OP-1抑制NTERA2的增殖并诱导其分化，其标志为细胞形态改变、胚胎癌细胞抗原（阶段特异性胚胎抗原3、阶段特异性胚胎抗原4、碱性磷酸酶肝同工酶）丧失以及新抗原出现，特别是阶段特异性胚胎抗原1和1类主要组织相容性复合体抗原。这些变化是不可逆的，且不涉及明显的细胞变性或细胞死亡。OP-1诱导的NTERA2分化似乎不同于视黄酸或六甲双乙酰胺诱导的分化。然而，OP-1确实诱导了同源盒基因HOXA1。相比之下，OP-1对无潜能性胚胎癌细胞系仅引发了有限的部分反应。
我们的结果表明，多能性人胚胎癌细胞对OP-1有反应而发生分化，并且该因子可以调节视黄酸诱导的分化。与转化生长因子-β超家族的其他成员一样，OP-1可能在早期胚胎中发挥诱导作用。结果还提示OP-1在某些生殖细胞肿瘤治疗中可能具有治疗价值。
