Comparison of BMP-2 and -4 for rat mandibular bone regeneration at various doses.
Comparison of BMP-2 and -4 for rat mandibular bone regeneration at various doses.
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DOI：
10.1111/j.1601-6343.2005.00349.x
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发表时间：
2005-11-01
影响因子：
3.1
通讯作者：
Collins, W
中科院分区：
文献类型：
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作者：
Arosarena, O;Collins, W
目的：比较不同剂量骨形态发生蛋白-2和-4 （BMP-2和-4）对下颌骨再生的影响。研究设计：在82只Sprague-Dawley大鼠的左半下颌骨上制造缺损。这些缺陷被透明质酸聚合物填充，透明质酸聚合物中含有0.01、0.1、1或10微米的BMP-2或-4。对照组由未填充缺陷的动物组成，或者用透明质酸海绵填充装有生长因子稀释缓冲液的缺陷。8周后处死动物，采用体视技术对半下颌骨进行组织学分析。结果：植入含有10 μ g BMP-2或-4载体的下颌骨在新骨面积方面与对照组有显著差异（p = 0.01和p = 0.0001）。骨髓空间发育以剂量依赖的方式发生（两种生长因子的p < 0.0001），并且在较大剂量下BMP-2的这种影响更为明显（1和10微克剂量的p < 0.0001）。新生骨面积和体积在生长因子之间没有显著差异。虽然植入BMP-4的缺损往往具有更厚的皮质骨和更多的骨小梁，但植入BMP-2的缺损（47%）比植入BMP-4的缺损（35%）至少实现了部分缺损桥接。结论：虽然BMP-2和bmp -4诱导的新骨面积和体积相似，但每种生长因子的成骨质量存在差异。结果表明，在该模型中，急性给药的阈值剂量为BMP-2的1至10微克，BMP-4的阈值剂量为>或=10微克。意义：这些发现提示骨生长因子成骨潜能的差异值得进一步研究，并可能对骨诱导蛋白治疗转化为临床实践产生影响。
OBJECTIVE: To compare mandibular bone regeneration with bone morphogenetic proteins-2 and -4 (BMP-2 and -4) at varying doses.STUDY DESIGN: Defects were created in the left hemi-mandibles of 82 Sprague-Dawley rats. The defects were filled with a hyaluronic acid polymer loaded with 0.01, 0.1, 1, or 10 microg of BMP-2 or -4. Control groups consisted of animals with unfilled defects, or with defects filled with the hyaluronic acid sponges loaded with growth factor dilution buffer. Animals were killed after 8 weeks, and the hemi-mandibles were analyzed histologically using stereologic techniques.RESULTS: Mandibles implanted with carriers containing 10 microg of BMP-2 or -4 differed significantly from controls in terms of new bone area (p = 0.01 and p = 0.0001, respectively). Marrow space development occurred in a dose-dependent fashion (p < 0.0001 for both growth factors), and this effect was more pronounced for BMP-2 at larger doses (p < 0.0001 at 1 and 10 microg doses). New bone areas and volumes did not differ significantly between the growth factors. While defects implanted with BMP-4 tended to have thicker cortical bone and more trabecular bone, at least partial defect bridging was achieved in a greater number of defects implanted with BMP-2 (47%) than with BMP-4 (35%).CONCLUSION: Although similar areas and volumes of new bone were induced with BMP-2 and -4, differences were noted in the quality of bone generated with each growth factor. The results indicate a threshold dose for acute administration between 1 and 10 mug BMP-2 for bony union in this model, and > or =10 microg for BMP-4.SIGNIFICANCE: These findings suggest that differences in bone growth factor osteogenic potential deserve further study and may have an impact on the translation of osteoinductive protein therapy into clinical practice.