Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7).
Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7).
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DOI：
10.3109/08977199609003228
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发表时间：
1996
期刊：
影响因子：
1.8
通讯作者：
U. Ripamonti;Barbara Van DenHeever;T. Sampath;M. Tucker;D. Rueger;A. Reddi
中科院分区：
文献类型：
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作者：
U. Ripamonti;Barbara Van DenHeever;T. Sampath;M. Tucker;D. Rueger;A. Reddi
我们检测了单独应用重组人成骨蛋白-1(HOP-1，骨形态发生蛋白-7)对成年雄性狒狒(Papio Ursinus)再生大的颅骨缺损的能力的效果。将重组的HOP-1与狒狒或牛鸟粪提取的不溶性胶原骨基质(0.1、0.5和2.5 mg/g胶原基质作为载体)联合植入手术制备的14只狒狒的46个颅骨缺损区，另18个缺损区植入未植入HOP-1的载体基质。分别于第15、30、90和365天取材，在连续的7微米未脱钙切片上进行组织形态计量学研究，以研究单独应用HOP-1后组织形态发生的时间顺序。组织学分析表明，HOP-1处理的标本在快速血管生成和间充质细胞向胶原基质迁移后，新骨形成的诱导过程是从周围到中心的。虽然软骨生成有限，但新形成的骨骼早在第15天就已经充满了完全分化的骨髓元素，即使是0.1毫克剂量的HOP-1也是如此。在30天和90天，0.1和0.5 mg剂量的HOP-1显示出比对照组更多的骨量，在90天，它们诱导了缺损区的完全再生。每克基质2.5 mg HOP-1诱导广泛成骨，最初表现为异位骨化和缺损区上方的颞肌移位。植入HOP-1一年后，颅骨内外皮质均恢复正常。这些结果表明，在成年灵长类动物中，HOP-1可以诱导颅骨的完全再生，提示HOP-1实现再生的最佳活性是每克基质中100-500微克的HOP-1。这些在灵长类动物中的研究结果可能为未来HOP-1的临床应用提供科学依据。
We examined the efficacy of a single application of recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7) for its ability to regenerate large calvarial defects in adult male baboons (Papio ursinus). Recombinant hOP-1, in conjunction with baboon or bovine guanidinium-extracted insoluble collagenous bone matrix (0.1, 0.5 and 2.5 mg per g of collagenous matrix as carrier), was implanted in 46 calvarial defects surgically prepared in 14 baboons, whilst 18 defects were implanted with the carrier matrix without hOP-1. Specimens were harvested on d 15, 30, 90 and 365 and subjected to histomorphometry on serial undecalcified sections cut at 7 microm to study the temporal sequence of tissue morphogenesis after the single application of hOP-1. Histological analysis indicated that the induction of new bone formation proceeded from the periphery to the central core of hOP-1 treated specimens after rapid angiogenesis and mesenchymal cell migration in apposition to the collagenous matrix. Whilst chondrogenesis was limited, newly formed bone has already filled with fully differentiated bone marrow elements as early as d 15, even with the 0.1 mg dose of hOP-1. On d 30 and 90, doses of 0.1 and 0.5 mg of hOP-1 showed greater amounts of bone than controls, and on d 90, they induced complete regeneration of the defects. Doses of 2.5 mg hOP-1 per g of matrix induced extensive osteogenesis initially with heterotopic ossification and displacement of the temporalis muscle above the defects. One year after implantation of hOP-1 there was restoration of the internal and external cortices of the calvaria. These results show that hOP-1 induces complete regeneration of calvarial bone in the adult primate, and suggest that the optimal activity of hOP-1 to achieve regeneration is between 100 and 500 microg of hOP-1 per g of matrix. These results in the primate may form the scientific basis for future clinical applications of hOP-1.