POTENT ECTOPIC BONE-INDUCING ACTIVITY OF BONE MORPHOGENETIC PROTEIN-4/7 HETERODIMER

POTENT ECTOPIC BONE-INDUCING ACTIVITY OF BONE MORPHOGENETIC PROTEIN-4/7 HETERODIMER
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DOI:
10.1006/bbrc.1995.1712
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发表时间:
1995-05-25
影响因子:
3.1
通讯作者:
FUJISAWA, Y
FUJISAWA, Y
中科院分区:
生物学4区
文献类型:
--
作者:
AONO, A;HAZAMA, M;FUJISAWA, Y

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我们纯化并鉴定了重组爪蟾骨形态发生蛋白(xBMPs):由杆状病毒表达系统产生的xbmp - 4,7的同型二聚体和异源二聚体(xBMP-4/7)。高纯度的xbmp具有同源的nh2末端,这是由一个共识基序Arg-X-X-Arg预测的,而它们具有不同的糖链。xBMPs与纯胶原载体一起植入大鼠,诱导新骨形成呈剂量依赖性。xBMP-4/7异源二聚体的活性最强,有效剂量为1 ~ 30 μ g,而xBMP-4或xbmp - 7同源二聚体的有效剂量大于10 μ g才有显著效果。组织学检查显示xBMP-4/7植入物显示膜内骨化,无软骨形成。在大鼠骨髓基质细胞原代培养中,xBMP-4/7诱导碱性磷酸酶的强度是xBMP-7的3倍,是xBMP-4的20倍。这些结果表明,在成人组织中,异二聚体形式的BMP会产生触发成骨细胞成骨分化的最强信号。(C) 1995学术出版社,Inc。
We have purified and characterized recombinant Xenopus bone morphogenetic proteins (xBMPs): homodimers of xBMP-4, 7 and heterodimers (xBMP-4/7) produced by a baculovirus expression system. Highly purified xBMPs had homogeneous NH2-termini predicted from a consensus motif, Arg-X-X-Arg, while they possessed diverse sugar chains. Implantation of xBMPs together with pure collagen carrier in rats induced new bone formation in a dose-dependent manner. The xBMP-4/7 heterodimer showed the strongest activity, with an effective dose of 1-30 mu g, while more than 10 mu g of xBMP-4 or 7 homodimer was required for a significant effect. Histological examination revealed that xBMP-4/7 implants showed intramembranous ossification without chondrogenesis. In primary cultures of rat bone marrow stromal cells, xBMP-4/7 induced alkaline phosphatase 3-fold more strongly than xBMP-7 and 20-fold more than xBMP-4. These results suggest that the heterodimeric form of BMP would generate the strongest signal triggering osteogenic differentiation of osteoprogenitor cells in adult tissues. (C) 1995 Academic Press, Inc.