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1.
Mast Cells Are Critical Regulators of Bone Fracture–Induced Inflammation and Osteoclast Formation and Activity 下载免费PDF全文
Jochen Kroner Anna Kovtun Julia Kemmler Joanna J Messmann Gudrun Strauss Sebastian Seitz Thorsten Schinke Michael Amling Johanna Kotrba Julia Froebel Jan Dudeck Anita Ignatius 《Journal of bone and mineral research》2017,32(12):2431-2444
Mast cells, important sensor and effector cells of the immune system, may influence bone metabolism as their number is increased in osteoporotic patients. They are also present during bone fracture healing with currently unknown functions. Using a novel c‐Kit‐independent mouse model of mast cell deficiency, we demonstrated that mast cells did not affect physiological bone turnover. However, they triggered local and systemic inflammation after fracture by inducing release of inflammatory mediators and the recruitment of innate immune cells. In later healing stages, mast cells accumulated and regulated osteoclast activity to remodel the bony fracture callus. Furthermore, they were essential to induce osteoclast formation after ovariectomy. Additional in vitro studies revealed that they promote osteoclastogenesis via granular mediators, mainly histamine. In conclusion, mast cells are redundant in physiologic bone turnover but exert crucial functions after challenging the system, implicating mast cells as a potential target for treating inflammatory bone disorders. © 2017 American Society for Bone and Mineral Research. 相似文献
2.
Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell–Derived IFN‐γ and CD40 Ligand In Vitro 下载免费PDF全文
Jianfei Qian Yuhuan Zheng Mingjun Zhang Enguang Bi Jin He Zhiqiang Liu Jingda Xu Jerry Y Gao Qing Yi 《Journal of bone and mineral research》2014,29(12):2666-2675
Osteoclasts (OCs) are bone resorbing cells whose activity can be regulated by activated T cells and their cytokines. However, the immune function of OCs is largely unknown. In this study, we found that as bystanders, human OCs effectively suppressed T‐cell proliferation induced by allogeneic, microbial antigenic, and T‐cell receptor stimuli in vitro. Mechanism studies revealed that T cell–derived IFN‐γ and CD40 ligand (CD40L) induced the expression of indoleamine 2,3‐dioxygenase (IDO) in OCs, which mediated the immunosuppressive function on T‐cell proliferation through depleting tryptophan. Neutralizing IFN‐γ and blocking CD40L, or silencing or inhibiting IDO in OCs restored T‐cell proliferation in the presence of OCs. Our data reveal a novel function of human OCs as inducible immunosuppressive cells, and a feedback loop between OCs and activated T cells. Thus, this study provides new insight into the mechanism of the immunosuppressive function of OCs, and may be helpful for developing novel therapeutic strategies for human diseases involving both the bone and immune systems. © 2014 American Society for Bone and Mineral Research. 相似文献