CHEMOATTRACTANTS & GROWTH FACTORS IN MINERALIZED TISSUES

这个项目试图在生物学上定义两类重要的 矿化组织中的活性蛋白：化学诱导剂和 增长因素。化学诱导剂的工作重点是骨骼和 牙本质基质蛋白，特别是骨钙素及其 在体外对单核细胞具有活性的组成多肽。 全骨的层析分离与定量 荧光法筛选趋化活性的研究 对于膜电位的变化将决定其贡献 并将揭示其他重要的分子物种 将对其进行提纯和表征。使用125I-骨钙素 单核细胞骨钙素受体将被共价标记并 已确认身份。确定受体与骨钙素的亲和力 相关合成肽是研究的前提信息 开发控制矿化组织的生化策略 人类的再吸收作用。 至少四类生长因子(PDGF、aFGFc、cFGFs和 转化生长因子-β)之前已经从 骨基质，利用肝素亲和层析作为 中心法。所有这些因子都是活跃的有丝分裂原 成骨细胞，毫无疑问地调节着发育，生长， 以及骨骼的重塑。另外三个矿化组织 对口腔至关重要(牙本质、牙釉质和 Cementum)将接受相同的分析以评估 生长因子在牙齿形成中的作用及其意义 依附于骨头。大鼠成骨细胞的生物合成研究， 成牙本质细胞和发育中的门牙的釉质器官 帮助确定与矩阵有关的增长因素的来源。 细胞实际生物学功能的测定 矿化组织中的化学诱导剂和生长因子必须 等待他们确切的化学描述，这是主要的 这个项目的目标。这一知识应该会直接产生 治疗和/或预防病理性疾病的益处 情况，包括骨质疏松症，骨化症，佩吉特氏病， 和口腔问题，涉及局限性骨丢失，牙槽骨隆起 正畸牙的牙根吸收与牙根吸收 有动静。

This project seeks to define two important classes of biologically active proteins in mineralized tissues: chemoattractants and growth factors. The chemoattractant work focuses on bone and dentin matrix proteins, particularly osteocalcin and its constituent peptides which are active on monocytes in vitro. Chromatographic separation and quantitation of total bone chemoattractant activity by screening with a fluorescence assay for membrane potential changes will determine the contribution of osteocalcin and will reveal other significant molecular species which will be purified and characterized. Using 125I-osteocalcin the monocyte osteocalcin receptor will be covalently labeled and identified. Defining the receptor's affinity for osteocalcin and related synthetic peptides is prerequisite information for developing biochemical strategies to control mineralized tissue resorption in humans. Growth factors of at least four classes (PDGF, aFGF, cFGF, and TGF-beta) have previously been purified and characterized from bone matrix, utilizing heparin affinity chromatography as a central method. All of these factors are active mitogens for osteoblasts and undoubtedly modulate the development, growth, and remodelling of bone. Three other mineralized tissues of critical importance to the oral cavity (dentin, enamel, and cementum) will be subjected to the same analysis to assess the relevance of growth factors in the formation of teeth and their attachment to bone. Biosynthesis studies with rat osteoblasts, odontoblasts, and the enamel organ of developing incisors will help to identify the sources of the matrix-bound growth factors. Determination of the actual biological functions of chemoattractants and growth factors in mineralized tissues must await their exact chemical description which is the principal objective of this project. This knowledge should yield direct benefits for the treatment and/or prevention of pathological conditions, including osteoporosis, osteopetrosis, Paget's disease, and oral problems involving localized bone loss, alveolar ridge resorption, and tooth root resorption during orthodontic tooth movement.