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

被引:220
作者
AONO, A [1 ]
HAZAMA, M [1 ]
NOTOYA, K [1 ]
TAKETOMI, S [1 ]
YAMASAKI, H [1 ]
TSUKUDA, R [1 ]
SASAKI, S [1 ]
FUJISAWA, Y [1 ]
机构
[1] TAKEDA CHEM IND LTD,DRUG SAFETY RES LABS,OSAKA 532,JAPAN
关键词
D O I
10.1006/bbrc.1995.1712
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:670 / 677
页数:8
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