Involvement of Osteocytes in the Action of Pasteurella multocida Toxin
Involvement of Osteocytes in the Action of Pasteurella multocida Toxin
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DOI：
10.3390/toxins10080328
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发表时间：
2018-08-01
期刊：
影响因子：
4.2
通讯作者：
Orth, Joachim H. C.
中科院分区：
文献类型：
--
作者：
Heni, Hannah;Ebner, Julia K.;Orth, Joachim H. C.
多杀性巴氏杆菌毒素（PMT）引起猪进行性萎缩性鼻炎伴严重鼻甲骨退化。据报道，毒素脱酰胺并激活异三聚体G蛋白，导致破骨细胞分化增加和成骨细胞分化受阻。迄今为止，PMT对骨组织中最丰富的细胞类型骨细胞的作用尚不清楚。在MLO-Y4骨细胞中，PMT脱酰胺异三聚体G蛋白，导致骨细胞树突过程丧失，应力纤维形成，细胞扩散和RhoC活化，但RhoA不活化。此外，毒素引起NF-B配体的膜结合受体激活剂（RANKL）加工释放可溶性RANKL，增强破骨细胞TNF-的分泌。在骨细胞和骨髓细胞共培养模型中，与单培养模型相比，pmt诱导的破骨细胞生成大大增加。在共培养中观察到的破骨细胞生成的增强被骨保护素隔离RANKL和抗TNF-抗体阻断，这表明破骨细胞因子的释放参与其中。数据支持骨细胞在骨代谢和破骨细胞发生中的关键作用，并确定骨细胞是进行性萎缩性鼻炎PMT的重要靶细胞。
Pasteurella multocida toxin (PMT) causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. It has been reported that the toxin deamidates and activates heterotrimeric G proteins, resulting in increased differentiation of osteoclasts and blockade of osteoblast differentiation. So far, the action of PMT on osteocytes, which is the most abundant cell type in bone tissue, is not known. In MLO-Y4 osteocytes, PMT deamidated heterotrimeric G proteins, resulting in loss of osteocyte dendritic processes, stress fiber formation, cell spreading and activation of RhoC but not of RhoA. Moreover, the toxin caused processing of membrane-bound receptor activator of NF-B ligand (RANKL) to release soluble RANKL and enhanced the secretion of osteoclastogenic TNF-. In a co-culture model of osteocytes and bone marrow cells, PMT-induced osteoclastogenesis was largely increased as compared to the mono-culture model. The enhancement of osteoclastogenesis observed in the co-culture was blocked by sequestering RANKL with osteoprotegerin and by an antibody against TNF- indicating involvement of release of the osteoclastogenic factors from osteocytes. Data support the crucial role of osteocytes in bone metabolism and osteoclastogenesis and identify osteocytes as important target cells of PMT in progressive atrophic rhinitis.