BONE CELL DIFFERENTIATION VIA CELL ADHESION

通过细胞粘附进行骨细胞分化

• 批准号: 6338642
• 负责人: LOUIS V AVIOLI
• 金额: $ 24.58万
• 依托单位: BARNES-JEWISH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338642
• 关键词: biological signal transduction; bone morphogenetic proteins; cell adhesion; cell cell interaction; cell differentiation; cell growth regulation; cell migration; chemokine; collagen; enzyme activity; fibroblast growth factor; fibronectins; human tissue; immunocytochemistry; immunoprecipitation; integrins; interleukin 8; laboratory mouse; mitogen activated protein kinase; osteoblasts; osteoclasts; osteogenesis; osteopontin; tissue /cell culture; transfection; transforming growth factors; tumor necrosis factor alpha

Skeletal remodeling is characterized by coordinated activities of osteoblasts and osteoclasts which are conditioned by matrix protein constituents, cell-cell interactions, and a variety of chemokine, cytokines, and growth factors. During the bone resorption process a variety of bone matrix constituents are released which serve to orchestrate bone remodeling via chemotaxis of osteoprogenitor cells to resorption sites and the stimulation, proliferation and differentiation of these cells into osteoblasts. Integrins have been implicated to play important roles in cell migration, target recognition, cell growth and differentiation in extraskeletal tissues. The role of cell surface integrins in either initiating and/or conditioning the coordinated osteoblastic component of the bone remodeling process, although ill- defined, is crucial since defective bone remodeling has been observed in transgenic animals with impaired integrin function in osteoblasts. The research proposed in this project is designed (i) to analyze the relationship of alphavbeta1, alphavbeta3 and alphavbeta5 integrins to osteoblast migration, adhesion, proliferation, and differentiation; (ii) to determine the signal transduction pathways which mediate the interaction between integrins and osteopontin, fibronectin, and type I collagen; and (iii) to study the effects of osteoblast inhibitory cytokines and chemokines (IL-8, TNF alpha and GRO) which are secreted by osteoclasts and specific osteogenic factors (bFGF, BMP-2, and TGF-beta) on the expression of integrins in osteoblasts and the roles of integrins in conditioning their effects on osteoblasts. The knowledge accumulated should clarify current concepts proposed to define mechanisms which control osteoblast development and activity, and also stimulate interest in developing new therapeutic modes for stimulating bone formation in disorders characterized by defective or deficient osteoblast activities. The acquired information should also further our knowledge with regard to the use of appropriate matrix proteins in orthopedic procedures where osteoblastic attachment is essential to guarantee normal bone formation and the integrity of either implanted bone tissue or porous non-osseous implants.

骨骼重塑的特点是协调活动， 由基质蛋白调节的成骨细胞和破骨细胞 成分，细胞-细胞相互作用，和各种趋化因子， 细胞因子和生长因子。在骨吸收过程中， 释放出各种骨基质成分 通过骨祖细胞的趋化性协调骨重建， 再吸收位点和刺激，增殖和分化 这些细胞转化成成骨细胞。整联蛋白被认为是 在细胞迁移、靶标识别、细胞生长和 外胚层组织分化。细胞表面的作用 整合素在启动和/或调节协调的 骨重建过程中的成骨细胞成分，虽然病- 定义，是至关重要的，因为有缺陷的骨重建已被观察到， 成骨细胞中整合素功能受损的转基因动物。的 本项目提出的研究旨在（i）分析 α v β 1、α v β 3和α v β 5整合素与 成骨细胞迁移、粘附、增殖和分化;（ii） 以确定介导细胞凋亡的信号转导途径。 整合素与骨桥蛋白、纤连蛋白和I型胶原之间的相互作用 胶原蛋白;和（iii）研究成骨细胞抑制剂的作用 细胞因子和趋化因子（IL-8、TNF α和GRO），其由 破骨细胞和特定的成骨因子（bFGF，BMP-2和TGF-β）， 整合素在成骨细胞中的表达及其在成骨细胞分化中的作用 调节它们对成骨细胞的影响。积累的知识 应澄清为界定机制而提出的现有概念， 控制成骨细胞的发育和活性，并激发兴趣 在开发新的治疗模式，刺激骨形成， 以成骨细胞活性缺陷或不足为特征的疾病。 所获得的信息还应进一步增进我们对以下方面的了解： 在整形外科手术中使用适当的基质蛋白， 成骨细胞附着是保证正常骨形成的必要条件 以及植入的骨组织或多孔非骨组织的完整性 植入物.