Pasteurella multocida toxin as a tool to modulate bone and immune cell differentiation

该项目将研究B细胞和破骨细胞分化之间的联系，使用来自多杀性巴氏杆菌（PMT）的细菌毒素作为模型系统。PMT是一种有效的有丝分裂原，具有已知的促骨细胞分化特性，分别刺激骨髓细胞分化为破骨细胞和抑制成骨细胞功能。本课题的目的是进一步阐明PMT诱导破骨细胞分化的机制，并明确B细胞在此过程中的作用。我们的目标是研究PMT产生的B细胞和破骨细胞群体及其相互作用或相互依赖。我们将通过表征分泌因子并通过比较PMT和IL 7、M-CSF/RANKL或LPS衍生的破骨细胞的分泌组和蛋白质组来在分子水平上研究这种相互作用的机制。此外，我们的目标是定义参与B细胞和破骨细胞之间的相互作用的信号网络，重点是通过Akt和Pim激酶的抗凋亡信号，以及迁移和粘附的重要性，以进一步扩大我们对免疫过程调节骨破坏的理解。

The project will investigate the connection between B-cell and osteoclast differentiation, using the bacterial toxin from Pasteurella multocida (PMT) as a model system. PMT is a potent mitogen with known osteoclastic properties that stimulates differentiation of bone marrow cells into osteoclasts and inhibits osteoblast function, respectively. The aim of the project is to further elucidate the mechanism of PMTinduced osteoclast differentiation and to define the role of B-cells in that process. We aim to characterise the PMT-generated B-cell and osteoclast populations and their interaction or dependence of each other. We will investigate the mechanism of that interaction on a molecular level by characterising the secreted factors and by comparing the secretome and proteome of PMT and IL7, M-CSF/RANKL or LPS derived osteoclasts. In addition, we aim to define the signalling networks involved in the interplay between B-cells and osteoclasts, with a focus on anti-apoptotic signalling through Akt and Pim kinases and the importance of migration and adhesion to further expand our understanding of the regulation of bone destruction by immunological processes.