Comparison of the osteogenic activity of bone morphogenetic protein (BMP) mutants
Comparison of the osteogenic activity of bone morphogenetic protein (BMP) mutants
复制标题
DOI：
10.1007/s10006-005-0644-2
复制
发表时间：
2005-11-01
影响因子：
1.8
通讯作者：
Wuerzler, K. K.
中科院分区：
文献类型：
--
作者：
Depprich, R.;Handschel, J.;Wuerzler, K. K.
背景：通过改变骨形态发生蛋白 2 (BMP-2) 的氨基酸序列来修饰肝素结合位点会导致局部保留时间的变化。本研究的目的是比较 T3 和 T4（两种与肝素结合能力增强的突变体）和 B2GDF-5（一种由 BMP-2 的 N 端氨基酸序列和 GDF-5 的 C 端序列与野生型 BMP-2 融合而产生的突变体）在体内的成骨活性。 材料和方法：将蛋白质与马源性胶原蛋白载体偶联，并植入成年大鼠标准化临界尺寸颅骨缺损中。 28天后，通过射线照相评估骨形成，并对新骨进行组织学表征。结果：蛋白质T3和T4显示出比BMP-2更高的成骨活性。与 BMP-2 型相比，GDF-5 和 B2GDF-5 观察到的新骨形成较少。 GDF-5和B2GDF-5之间没有观察到骨形成存在差异。结论：肝素结合能力的增加增强了BMP2体内的成骨活性。这可能是由于在组织中的保留时间较长，从而具有更好的生物利用度。用BMP-2的相应序列替换GDF-5的N端氨基酸序列并没有导致成骨活性增加，因为肝素结合能力不是GDF-5生物利用度的主要原因。
Background: Modification of the heparin binding site by alteration of the amino acid sequence of bone morphogenetic protein-2 (BMP-2) results in a change in the local retention time. The purpose of this study was to compare the osteogenic activity of T3 and T4, two mutants with increased binding capacity to heparin, and B2GDF-5 a mutant resulting from the fusion of the n-terminal amino acid sequence of BMP-2 and the c-terminal sequence of GDF-5 with wild-type BMP-2 in vivo.Material and methods: The proteins were coupled to an equine-derived collagen carrier and implanted in standardized critical size calvarial defects in adult rats. After 28 days, bone formation was evaluated radiographically and the new bone was characterized histologically.Results: Proteins T3 and T4 showed a higher osteogenic activity than BMP-2. Less new bone formation was observed with GDF-5 and B2GDF-5 than with-type BMP-2. No difference in bone formation was observed between GDF-5 and B2GDF-5.Conclusion: Increased heparin binding capacity enhances osteogenic activity of BMP2 in vivo. This might be due to a longer retention period in the tissue and thus better bioavailability. Replacement of the N-terminal amino acid sequence of GDF-5 by the corresponding sequence of BMP-2 did not result in an increased osteogenic activity as heparin binding capacity is not the main reason for the bioavailability of GDF-5.