麻风杆菌及NOD2通过铁调素致麻风患者牙槽骨吸收机制研究

Leprosy is a chronic infectious disease that seriously endangers human health. The interaction between Mycobacterium leprae and its susceptibility genes determine the incidence of the disease. Our previous study found that leprosy patients usually accompanied severe alveolar bone resorption and high expression of hepcidin in skin lesions which is closely related to bone metabolism. Based on the above, we propose the scientific hypothesis: M. leprae and NOD2 can aggravate the alveolar bone resorption in leprosy patients by regulating the expression of hepcidin. In this project, we will examine the bone resorption and the expression of hepcidin in leprosy patients and explore the expression of hepcidin and osteoclast-related cytokines during osteoclastogenesis by obtaining the α antigen of M. leprae or over-expressing/knockouting NOD2 gene in vitro. To further verify the above mechanism, we will use the hepcidin-knockout mice combined with mimicing leprosy infection or not. In a word, this study will discuss the possible mechanism of bone resorption in leprosy patients, and provide a theoretical basis to find new molecular targets and treatment strategies for preventing bone resorption of leprosy patients.

麻风是严重危害人类健康的慢性感染性疾病。麻风杆菌和易感基因的相互作用共同决定了疾病的发生。我们前期研究发现麻风患者伴有较严重的牙槽骨吸收，并且其皮损中与骨代谢密切相关的铁调素表达明显升高。因此，我们提出科学问题：麻风杆菌是否可协同其易感基因NOD2通过调节铁调素的表达参与麻风患者的牙槽骨吸收。本研究拟检测麻风患者牙槽骨吸收及铁调素表达情况，利用体外获得的麻风杆菌有效成分α抗原蛋白、Nod2基因敲除/过表达，探索其在单核巨噬细胞诱导破骨生成过程中破骨相关因子及铁调素的表达与机制，进一步在模拟麻风杆菌感染的铁调素基因敲除小鼠中验证。探讨麻风患者牙槽骨吸收的可能机理，为防治麻风患者牙槽骨吸收寻找新的分子靶点和治疗策略提供理论依据。

麻风是严重危害人类健康的慢性感染性疾病。麻风杆菌和易感基因的相互作用共同决定了疾病的发生。我们前期研究发现麻风患者伴有较严重的牙槽骨吸收，并且其皮损中与骨代谢密切相关的铁调素表达明显升高。因此，我们提出科学问题：麻风杆菌是否可协同其易感基因NOD2通过调节铁调素的表达参与麻风患者的牙槽骨吸收。本研究拟检测麻风患者牙槽骨吸收及铁调素表达情况，利用体外获得的麻风杆菌有效成分α抗原蛋白、NOD2基因敲除/过表达，探索其在单核巨噬细胞诱导破骨生成过程中破骨相关因子及铁调素的表达与机制，进一步在模拟麻风杆菌感染的铁调素基因敲除小鼠中验证。探讨麻风患者牙槽骨吸收的可能机理，为防治麻风患者牙槽骨吸收寻找新的分子靶点和治疗策略提供理论依据。麻风患者病例收集后风发现治愈者血清中的Col1α2表达水平比健康男性低，麻风治愈者四肢存在不同程度的溃疡，在体内水平证实了麻风杆菌感染可致NF-κB的表达升高，从而促进铁调素的表达，破骨相关标志物表达上升，同时体外实验验证不同类型的MDP对骨代谢的影响发现MDP 可激活MLO-Y4中的miR-342-3p表达谱，miR-342-3p与Col1α2表达负相关；MDP可影响小鼠原代成骨细胞中Col1α2表达，经MDP处理过的MLO-Y4的条件性培养液，影响成骨细胞的成骨分化指标；对MDP干预骨细胞后构建的 circRNA与mRNA芯片进行GO分析，KEGG分析以及绘制了String网络关系图。通过体内外实验证实了麻风杆菌可协同其易感基因NOD2通过调节铁调素的表达参与麻风患者的牙槽骨吸收，并发现miR-342-3p参与其相关调控信号通路。

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