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

该项目将以多杀性巴氏杆菌的细菌毒素(PMT)为模型系统，研究B细胞和破骨细胞分化之间的联系。PMT是一种有效的有丝分裂原，具有已知的破骨特性，分别刺激骨髓细胞分化为破骨细胞和抑制成骨细胞功能。该项目的目的是进一步阐明PMT诱导破骨细胞分化的机制，并确定B细胞在这一过程中的作用。我们的目标是描述PMT产生的B细胞和破骨细胞群体以及它们之间的相互作用或依赖。我们将通过比较PMT和IL7、M-CSF/RANKL或脂多糖来源的破骨细胞的分泌组和蛋白质组，从分子水平上探讨这种相互作用的机制。此外，我们的目标是确定参与B细胞和破骨细胞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黏附的重要性，以进一步扩大我们对免疫过程对骨破坏调控的理解。

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.