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重组人骨形态发生蛋白-2与自体、异体和异种骨移植联合使用的有效性。

Effectiveness of rhBMP-2 association to autogenous, allogeneic, and heterologous bone grafts.

作者信息

Gonzaga Miliane Gonçalves, Dos Santos Kotake Bruna Gabriela, de Figueiredo Fellipe Augusto Tocchini, Feldman Sara, Ervolino Edilson, Dos Santos Maria Cecília Gorita, Issa João Paulo Mardegan

机构信息

Ribeirão Preto Medical School, Department of Biomechanics, Medicine and Rehabilitation of Locomotor, University of São Paulo, São Paulo, Brazil.

School of Medicine, LABOATEM - Osteoarticular Biology, Tissue Engineering and Emerging Therapies Laboratory, National Rosario University, Santa Fe, Argentina.

出版信息

Microsc Res Tech. 2019 Jun;82(6):689-695. doi: 10.1002/jemt.23215. Epub 2019 Jan 14.

Abstract

Proteins with osteoinductive potential, especially recombinant human bone morphogenetic protein (rhBMP)-2, have large effects on cell growth and their differentiation. The aim of this study was to assess repair of bone defects in rat calvaria with different types of grafts associated with rhBMP-2, through immunohistochemistry and micro computed tomography (CT) analyses. A total of 35 male Wistar rats were selected, each weighing ~250 g, with a waiting period of 6 weeks from the creation of the defect to the sacrifice, and divided into five groups (n = 7): autograft plus 5 μg rhBMP-2 (AuG/BMP-2); allograft plus 5 μg rhBMP-2 (AlG/BMP-2); xenograft (heterologous) plus 5 μg rhBMP-2 (XeG/BMP-2); 5 μg rhBMP-2 (BMP-2) and the control group (n = 7). The micro CT reveal that all groups associating different bone grafts with BMP-2 showed increased bone formation compared to the control. The immunostaining show that osteocalcin and bone sialoprotein were higher in groups with BMP-2 than control group; BMP was high expressed in AuG/BMP-2, AlG/BMP-2, and BMP-2; vascular endothelial growth factor (VEGF) was more expressed in groups with BMP-2; VEGF-R2 was low to moderate in AuG/BMP-2, XeG/BMP-2, and BMP-2, predominantly moderate in AlG/BMP-2 and low in the control; CD-31 was predominantly moderate in AuG/BMP-2, AlG/BMP-2, and XeG/BMP-2, low to moderate in BMP-2 and low in the control. The results revealed that rhBMP-2 improved bone repair when administered alone, or when associated with different bone grafts.

摘要

具有骨诱导潜力的蛋白质,尤其是重组人骨形态发生蛋白(rhBMP)-2,对细胞生长及其分化有很大影响。本研究的目的是通过免疫组织化学和微型计算机断层扫描(CT)分析,评估与rhBMP-2相关的不同类型移植物对大鼠颅骨骨缺损的修复情况。共选择35只雄性Wistar大鼠,每只体重约250 g,从缺损形成到处死的等待期为6周,并分为五组(n = 7):自体移植加5 μg rhBMP-2(AuG/BMP-2);同种异体移植加5 μg rhBMP-2(AlG/BMP-2);异种移植(异源)加5 μg rhBMP-2(XeG/BMP-2);5 μg rhBMP-2(BMP-2)以及对照组(n = 7)。微型CT显示,与对照组相比,所有将不同骨移植物与BMP-2联合使用的组均显示骨形成增加。免疫染色显示,与对照组相比,BMP-2组的骨钙素和骨唾液蛋白含量更高;BMP在AuG/BMP-2、AlG/BMP-2和BMP-2组中高表达;血管内皮生长因子(VEGF)在BMP-2组中表达更高;VEGF-R2在AuG/BMP-2、XeG/BMP-2和BMP-2组中低至中度表达,在AlG/BMP-2组中主要为中度表达,在对照组中为低表达;CD-31在AuG/BMP-2、AlG/BMP-2和XeG/BMP-2组中主要为中度表达,在BMP-2组中低至中度表达,在对照组中为低表达。结果表明,rhBMP-2单独给药或与不同骨移植物联合使用时均可改善骨修复。

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