ROLE OF DIFFERENTIATION FACTORS IN CARTILAGE AND BONE FORMATION AND REGENERATION

这个项目的目标是研究软骨和骨骼。 并确定它们在胚胎发生和发育中的作用。 出生后的生命，包括组织形成和疾病。作为组织 再生概括了胚胎的发育顺序 组织形成，可以想象的是，了解 可溶性分化因子的作用是迈向 骨骼组织的生物控制再生。这将是 对先天性和/或获得性心脏病的治疗有重大影响 骨骼疾病，如巨大的骨缺损，骨折愈合不良， 骨关节炎、骨质疏松症和牙周炎。这个项目的重点是 软骨和骨诱导分子的进一步表征 以及它们的结合蛋白。具有软骨诱导作用的蛋白质组分 体内活性，已从关节软骨和 纯化至均一；胰蛋白酶多肽的蛋白质测序数据 数据库搜索没有发现与任何 已知的序列。新蛋白的组织特异性定位 使用多克隆抗体进行免疫定位，显示制备方法 对照N-末端序列。通过cDNA进一步鉴定 克隆技术正在进行中。将分子探针用于最近的 骨形态发生蛋白的特征，我们正在研究它们 对软骨、软骨内和膜骨的贡献 队形。免疫组织化学定位与原位杂交 软骨和骨诱导蛋白，以及体外研究， 表明这些分子对引发的选择性贡献， 增强、维持和成熟软骨细胞和 成骨细胞表型。这项工作对基础工作的贡献 了解新生软骨和骨形成，并设置 适当指示和使用这些可溶分化的阶段 临床环境中的因素。

The objectives of this project are to study the cartilage and bone inducing factors and to define their role in embryogenesis and in postnatal life, both in tissue formation and in disease. As tissue regeneration recapitulates the developmental sequence of embryonic tissue formation, it is conceivable that understanding the mechanisms of action of the soluble differentiation factors is a key step towards biologically controlled regeneration of skeletal tissues. This will have a significant impact on the treatment of congenital and/or acquired skeletal diseases such as large bone defects, impaired fracture healing, osteoarthritis, osteoporosis and periodontitis. This project focuses on the further characterization of cartilage and bone inducing molecules and their binding proteins. Protein fractions with cartilage inducing activity in vivo, have been isolated from articular cartilage and purified to homogeneity; protein sequencing data from tryptic peptides have been obtained; databank searches did not reveal homology with any known sequences. The tissue specific localization of the new protein preparation was shown by immunolocalization using a polyclonal antibody against the N-terminal sequence. Further characterization by cDNA cloning is in progress. Using the molecular probes for the recently characterized bone morphogenetic proteins, we are studying their respective contribution to cartilage, endochondral and membranous bone formation. Immunohistochemical localization and in situ hybridization of cartilage and bone inducing proteins, as well as studies in vitro, indicate the selective contribution of these molecules to initiation, enhancement, maintenance and maturation of the chondrocytic and osteoblastic phenotype. This work contributes to the basic understanding of de novo cartilage and bone formation, and sets the stage for the proper indication and use of these soluble differentiation factors in a clinical setting.