MECHANISM OF ASEPTIC LOOSENING--AN IN VITRO STUDY

该项目的长期目标是改进骨水泥关节成形术。 通过避免或延缓无菌松动的发生来延长寿命 将：1)将骨水泥关节置换术的适应症扩大到更年轻的人群 个人，2)避免或推迟所有翻修手术的需要 患者，3)改善那些骨质量较差的患者的结果 或数量。为了达到这个目标，这个项目的具体目标 是为了提高我们对无菌松动机理的理解。 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，我们将确定以下角色 每种细胞类型都存在于骨-骨水泥界面(即成骨细胞， 破骨细胞、巨噬细胞)在导致无菌的骨吸收中 PMMA颗粒与大鼠巨噬细胞共培养的松动作用 颅骨及~(45)Ca释放的测定：2.牙本质上的破骨细胞 通过扫描电子显微镜测量骨中的开挖条带和数量，3. 首先是成骨细胞，然后加入新的二次条件 培养液：a.大鼠颅骨测量45Ca释放量，b. 牙本质条上培养的破骨细胞及其挖掘量的测量 在第二组研究中，我们将 确定三种主要骨吸收的相对作用 通过重复实验在界面处调节骨吸收的介体 在组1中，并试图阻止45Ca释放或破骨细胞挖掘 使用；1.吲哚美辛(阻断前列腺素E_2合成)，2.抗体 肿瘤坏死因子和3.白介素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.