MECHANISM OF ASEPTIC LOOSENING--AN IN VITRO STUDY

该项目的长期目标是改善骨水泥关节成形术 通过避免或延迟无菌性松动的发生， 将：1）将骨水泥型关节置换术的适应症扩大到年轻人 个体，2）避免或延迟所有翻修手术的需要 患者，3）改善骨质差患者的结果 或数量。 为达到这一目标，本项目的具体目标 是为了提高我们对无菌性松动机制的理解。 这将是一项体外研究，涉及两组实验， 五年的时间。 在第一组中，我们将确定 存在于骨-水泥界面的每种细胞类型（即成骨细胞， 破骨细胞，巨噬细胞）的骨吸收，导致无菌 通过将暴露于PMMA颗粒的巨噬细胞与以下物质共培养而松动：1.大鼠 测量45 Ca释放;牙本质表面培养的破骨细胞 通过扫描E.M.测量骨中的挖掘数量，3. 首先是成骨细胞，然后加入新的二次条件 媒体：a.大鼠颅骨并测量45 Ca释放，以及; B. 在牙本质条上培养破骨细胞并测量凹陷数 在骨头里找到了一个小洞 在第二组研究中， 确定三种主要骨吸收中每一种的相对作用 通过重复实验， 第1组，尝试阻断45个Ca释放或破骨细胞的挖掘 与; 1。吲哚美辛（阻断前列腺素E2合成），2.抗体 肿瘤坏死因子和3.白细胞介素1抗体。

The long term objective of this project is to improve cemented arthroplasty longevity by avoiding or delaying the occurrence of aseptic loosening which would: 1) broaden the indications for cemented arthroplasty to younger individuals, 2) avoid or delay the need for revision surgery in all patients, 3) improve results in those patients who have poor bone quality or quantity. To obtain this objective, the specific goal of this project is to improve our understanding of the mechanism of aseptic loosening. This will be an in - vitro study involving two groups of experiments over a five year period. In the first group, we will determine the role for each cell type present at the bone-cement interface (i.e. osteoblast, osteoclast, macrophage) in the bone resorption that leads to aseptic loosening by coculturing macrophages exposed to PMMA particles with: 1. rat calvaria and measuring 45 Ca release, 2. osteoclasts cultured on dentin strips and measuring numbers of excavations in bone via scanning E.M., 3. first with osteoblasts and then adding the new secondarily conditioned media to: a. rat calvaria and measuring 45 Ca release, and to; b. osteoclasts cultured on dentin strips and measuring numbers of excavations in bone via scanning E.M. In the second groups of studies, we will determine the relative role of each of the three major bone resorbing mediators in bone resorption at the interface by repeating the experiments in group 1 and attempting to block 45 Ca release or osteoclast excavations with; 1. indomethacin (block prostaglandin E2 synthesis), 2. antibodies to tumor necrosis factor and 3. antibodies to interleukin 1.