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Toxins 2018, 10(8), 328; https://doi.org/10.3390/toxins10080328

Involvement of Osteocytes in the Action of Pasteurella multocida Toxin

1
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany
2
Hermann-Staudinger-Graduiertenschule, Universität Freiburg, 79104 Freiburg, Germany
3
Spemann Graduate School of Biology and Medicine (SGBM), Universität Freiburg, 79104 Freiburg, Germany
4
Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany
5
BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Received: 25 July 2018 / Revised: 6 August 2018 / Accepted: 8 August 2018 / Published: 13 August 2018
(This article belongs to the Section Bacterial Toxins)
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Abstract

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-κB ligand (RANKL) to release soluble RANKL and enhanced the secretion of osteoclastogenic TNF-α. 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-α 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. View Full-Text
Keywords: Pasteurella multocida toxin (PMT); deamidation; osteocytes; osteoclastogenesis Pasteurella multocida toxin (PMT); deamidation; osteocytes; osteoclastogenesis
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Heni, H.; Ebner, J.K.; Schmidt, G.; Aktories, K.; Orth, J.H.C. Involvement of Osteocytes in the Action of Pasteurella multocida Toxin. Toxins 2018, 10, 328.

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