ROLE OF DIFFERENTIATION FACTORS IN CARTILAGE AND BONE FORMATION AND REGENERATION

本项目的目标是研究软骨和骨 诱导因子，并确定它们在胚胎发生和 在组织形成和疾病中的作用。诸如组织 再生再现了胚胎的发育顺序 组织形成，可以想象，理解的机制， 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 对治疗先天性和/或后天性 骨骼疾病如大的骨缺损，受损的骨折愈合， 骨关节炎、骨质疏松症和牙周炎。 该项目的重点是 软骨和骨诱导分子的进一步表征 及其结合蛋白。具有软骨诱导的蛋白质组分 体内活性，已经从关节软骨中分离出来， 纯化至均一;来自胰蛋白酶肽的蛋白质测序数据 已经获得;数据库搜索没有发现任何同源性 已知序列。新蛋白的组织特异性定位 通过使用多克隆抗体的免疫定位显示制备 与N-末端序列相比较。通过cDNA进一步表征 克隆正在进行中。 利用分子探针， 骨形态发生蛋白，我们正在研究它们的 分别对软骨、软骨内骨和膜骨的贡献 阵 免疫组织化学定位和原位杂交 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、维持和成熟的软骨细胞， 成骨细胞表型 这项工作有助于基本的 了解从头软骨和骨形成，并设置 这些可溶性分化的适当指示和使用的阶段 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.