DCs经纳米级UHMWPE诱导后促进巨噬细胞分化为破骨细胞的作用机制研究

Osteolysis around the prosthesis which was induced by the wear particles is the main reason of aseptic loosening of prosthesis. It may eventually lead to the failure of the prosthesis, and serious impact on the long-term effect of the artificial joint replacement. Ultra high molecular weight polyethylene (UHMWPE) are the most common wear particles. It was generally accepted that wear particles promote the formation of osteoclasts and bone resorption through the activation of macrophages. However, the underlined mechanism is still not completely defined. UHMWPE nano particles are recognized involved in the differentiation of osteoclast precursor cells into osteoclasts. However, the related research reports are rare. In our previous published studies, we have found that UHMWPE particles can induce osteoclast Raw264.7 differentiation, and this effect can be strengthened with the co-culture of dendritic cells DC2.4. This project intends to respectively down-regulate DC2.4 cell E2F1 gene expression by siRNA interference and GM-CSF intervention, to investigate the differentiation of the macrophage into osteoclasts, which may illustrate the role of DC2.4 and GM-CSF in osteoclast differentiation stage.

由磨损颗粒诱导的假体周围骨溶解是导致假体无菌性松动并最终引发假体失效的最主要原因，严重影响人工关节置换术的远期疗效。磨损颗粒中以超高分子量聚乙烯(UHMWPE)居多，一般认为，磨损颗粒通过激活巨噬细胞，进而促进破骨细胞的生成和骨吸收。然而，其具体发生机制尚未完全清楚。随着纳米级UHMWPE微粒的发现，纳米UHMWPE微粒参与破骨前体细胞分化为破骨细胞开始被关注，但仍处起步阶段，国内外相关研究报道少见。本项目在前期已发表研究中，发现UHMWPE颗粒可诱导巨噬细胞Raw 264.7分化为破骨细胞，并且，该作用可在树突状细胞DC2.4共培养时加强。本项目拟分别通过SiRNA干扰下调DC2.4细胞E2F1基因的表达和GM-CSF干预的手段，研究巨噬细胞分化为破骨细胞过程中的影响，进而阐明DC2.4和GM-CSF在破骨细胞分化前体阶段的相关机制。

由磨损颗粒诱导的假体周围骨溶解是导致假体无菌性松动并最终引发假体失效的最主要原因，严重影响人工关节置换术的远期疗效。磨损颗粒中以超高分子量聚乙烯(UHMWPE)居多，一般认为，磨损颗粒通过激活巨噬细胞，进而促进破骨细胞的生成和骨吸收。然而，其具体发生机制尚未完全清楚。随着纳米级UHMWPE微粒的发现，纳米UHMWPE微粒参与破骨前体细胞分化为破骨细胞开始被关注，但仍处起步阶段，国内外相关研究报道少见。本项目研究发现，UHMWPE颗粒可诱导巨噬细胞Raw 264.7分化为破骨细胞，并且，该作用可在树突状细胞DC2.4共培养时加强。本项目通过SiRNA干扰下调DC2.4细胞E2F1基因的表达和GM-CSF干预的手段，研究巨噬细胞分化为破骨细胞过程中的影响，进而阐明DC2.4和GM-CSF在破骨细胞分化前体阶段的相关机制。