RECOMBINANT BMP AND BONE FORMATION

骨形成受全身激素和局部生长因子的调节 它们影响骨细胞的复制和分化。这块骨头 形态发生蛋白(BMP)是一种骨诱导蛋白，它是 最初是通过脱矿骨萃取物中存在的它们来鉴定的。 该家族至少有六名亲属已被确认为 分子克隆被称为BMP-2到BMP-7。这些分子是 基于初级氨基酸序列的部分转化生长因子β超家族 同源性(Rosen和Thies，1992)。骨形态发生蛋白具有骨诱导活性 性质，并能够诱导形成新的软骨和 在啮齿动物测试系统中异位植入或与 体内骨折愈合模型。 假设成骨细胞是从多潜能基质发展而来的。 骨髓中的干细胞。这项研究提案的目标是 为了确定将BMP基因(即BMP-2)导入到 骨髓基质细胞会将基质细胞转化为 骨祖细胞，2)显示自分泌环的存在 通过激活内源性BMP基因获得BMP。最初的实验 在这项拟议的研究中，将检查BMP对生长的影响 基质细胞和纤维蛋白原细胞在体外培养中的分化 系统。各种连续基质细胞系和成纤维细胞系将被 测试过。这些细胞系将被含有逆转录病毒的BMP-2感染 向量。 如果文化研究是成功的，那么就适合进行测试 这些概念在活体啮齿动物骨折模型中。这些区别在于 基质和成纤维蛋白细胞系，可以提供持续的局部 在骨折部位产生的骨形态发生蛋白将用于骨愈合。 叛逃。这项研究将加深我们对这一关系的理解 转化生长因子-β超家族与骨生长发育 骨折修复。

Bone formation is regulated by systemic hormones and local growth factors which influence bone cell replication and differentiation. The bone morphogenetic proteins (BMP) are osteoinductive proteins which were originally identified by their presence in extracts of demineralized bone. At least six related members of this family have been identified by molecular cloning and are called BMP-2 through BMP-7. These molecules are part of the TGFbeta superfamily based on primary amino acid sequence homology (Rosen and Thies, 1992). The BMPs possess osteoinductive properties and are capable of inducing the formation of new cartilage and bone when implanted ectopically in a rodent assay system or when used with in vivo fracture healing models. It is hypothesized that osteoblasts develop from a multi-potential stromal stem cell in the bone marrow. The objective of this research proposal is to determine if the introduction of the gene for BMP (i.e. BMP-2) into bone marrow stromal cells will 1) transform the stromal cells into osteoprogenitor cells, 2) demonstrate the presence of an autocrine loop for BMP by activation of an endogenous BMP gene. The initial experiments in this proposed study would examine the influence of BMP on the growth and differentiation of stromal and fibroplastin, cells in an vitro culture system. Various continuous stromal cell lines and fibroblast lines will be tested. These cell lines will be infected by a BMP-2 containing retroviral vector. If the culture studies are successful it would then be appropriate to test these concepts in an in vivo rodent fracture model. These differentiated stromal and fibroplastin cell lines which can provide sustained local production of BMP at the fracture site will be employed to heal a bone defect. This research will increase our understanding of the relationship between the TGF-beta superfamily and bone growth and development and fracture repair.