BONE CELL DIFFERENTIATION VIA CELL ADHESION

骨骼重塑的特点是协调活动 受基质蛋白调节的成骨细胞和破骨细胞 成分、细胞间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 释放多种骨基质成分，有助于 通过骨祖细胞的趋化作用协调骨重塑 吸收位点和刺激、增殖和分化 这些细胞转化为成骨细胞。整合素与发挥作用有关 在细胞迁移、目标识别、细胞生长和 骨外组织的分化。细胞表面的作用 整合素在启动和/或调节协调 骨重塑过程中的成骨细胞成分，尽管有缺陷 定义，是至关重要的，因为在以下部位观察到有缺陷的骨重塑 成骨细胞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 alphavbeta1、alphavbeta3 和 alphavbeta5 整合素与 成骨细胞迁移、粘附、增殖和分化； (二) 以确定介导的信号转导途径 整合素与骨桥蛋白、纤连蛋白和 I 型之间的相互作用 胶原蛋白； (iii) 研究成骨细胞抑制的作用 细胞因子和趋化因子（IL-8、TNF α 和 GRO） 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中的作用 调节它们对成骨细胞的影响。所积累的知识 应澄清目前提出的概念，以定义机制， 控制成骨细胞的发育和活性，并激发兴趣 开发刺激骨形成的新治疗模式 以成骨细胞活性缺陷或不足为特征的疾病。 所获得的信息还应该进一步加深我们对以下方面的认识： 在整形外科手术中使用适当的基质蛋白，其中 成骨细胞附着对于保证正常骨形成至关重要 以及植入骨组织或多孔非骨组织的完整性 植入物。

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.