Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo
Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo
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DOI：
10.3109/08977199609003229
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发表时间：
1996-01-01
期刊：
影响因子：
1.8
通讯作者：
Wozney, JM
中科院分区：
文献类型：
--
作者：
Israel, DI;Nove, J;Wozney, JM
骨形态发生蛋白 (BMP) 是 TGF-β 基因超家族的一个亚组，是参与多种组织生长、分化和修复的二聚体分子。基于从牛骨中分离出几种 BMP 时共纯化以及小鼠胚胎发生过程中存在共定位模式的观察，我们在中国仓鼠卵巢细胞中共表达 BMP 的各种组合，以测试可能的异二聚体形成和活性。 BMP-2 与 BMP-5、BMP-6 或 BMP-7 瞬时共表达，或 BMP-4 与 BMP-7 瞬时共表达，比任何单一 BMP 的表达产生更多的 BMP 活性。然后制备稳定细胞系，以便更详细地纯化和表征共表达的 BMP。 BMP-2 与 BMP-7 的共表达产生异二聚体 BMP-2/7，在体外碱性磷酸酶诱导测定中，其比活性比 BMP 同二聚体高约 20 倍。在体内测定中，这些异二聚体在诱导软骨和骨方面比 BMP-2 更有效 5 至 10 倍。 BMP-2/6 异二聚体也获得了类似的结果。这些实验证明了几种 BMP 异二聚体相对于 BMP 同二聚体的效力增强，并支持这样的假设：此类异二聚体形式可能具有天然生物学功能。
The bone morphogenetic proteins (BMPs), a subgroup of the TGF-beta gene super-family, are dimeric molecules involved in the growth, differentiation and repair of a wide variety of tissues. Based on the observation that several of the BMPs co-purify when isolated from bovine bone and that a pattern of co-localization exists during mouse embryogenesis, we co-expressed various combinations of BMPs in Chinese hamster ovary cells to test for possible heterodimer formation and activity. Transient co-expression of BMP-2 with either BMP-5, BMP-6 or BMP-7, or BMP-4 transiently co-expressed with BMP-7, resulted in more BMP activity than expression of any single BMP. Stable cell lines were then made in order to purify and characterize co-expressed BMPs in more detail. Co-expression of BMP-2 with BMP-7 yielded heterodimeric BMP-2/7 with a specific activity about 20-fold higher than BMP homodimers in an in vitro alkaline phosphatase induction assay. These heterodimers were also 5- to 10-fold more potent than BMP-2 in inducing cartilage and bone in an in vivo assay. Similar results were obtained with BMP-2/6 heterodimer. These experiments demonstrate the increased potency of several BMP heterodimers relative to BMP homodimers and support the hypothesis that such heterodimeric forms are likely to have natural biological functions.