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Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice

Bertrand, J, Nitschke, Y, Fuerst, M, Hermann, S, Schäfers, M, Sherwood, J, Nalesso, G, Ruether, W, Rutsch, F, Dell'Accio, F and Pap, T (2012) Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice Annals of the Rheumatic Diseases.

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Abstract

Objective To analyse the function of nucleotide pyrophosphatase phosphodiesterase (NPP1), a member of the pyrophosphate pathway, in osteoarthritis (OA). Methods mRNA expression of NPP1, ANK ankylosing protein and tissue non-specific alkaline phosphatase was assessed by quantitative PCR. NPP1 protein levels were analysed in mouse and human cartilage samples. Bone metabolism was analysed by F18-positron emission tomography-scanning and µCT in ttw/ttw mice. Ttw/ttw mice are mice carrying a loss-of-function mutation in NPP1. Calcification of articular cartilage was assessed using von Kossa staining and OA severity using the Mankin score. Cartilage remodelling was investigated by type X collagen immunohistochemistry. Results Expression of NPP1, but not the other members of this pathway, inversely correlated with cartilage calcification and OA severity in mouse and humans. Proinflammatory cytokines downregulated the expression of NPP1, demonstrating an influence of inflammation on matrix calcification. Ttw/ttw mutant mice, carrying a loss-of-function mutation in NPP1, exhibit increased bone formation process in joints compared with wild types. Ttw/ttw mice also developed spontaneous OA-like changes, evaluated by histological analysis and in vivo imaging. Ectopic calcifications were associated with increased expression of collagen X in the cartilage. Conclusion The authors conclude that OA is characterised by the reactivation of molecular signalling cascades involving proinflammatory cytokines, thereby regulating the pyrophosphate pathway which consequently leads to cartilage ossification, at least in part resembling endochondral ossification.

Item Type: Article
Subjects : Veterinary Medicine
Authors :
NameEmailORCID
Bertrand, JUNSPECIFIEDUNSPECIFIED
Nitschke, YUNSPECIFIEDUNSPECIFIED
Fuerst, MUNSPECIFIEDUNSPECIFIED
Hermann, SUNSPECIFIEDUNSPECIFIED
Schäfers, MUNSPECIFIEDUNSPECIFIED
Sherwood, JUNSPECIFIEDUNSPECIFIED
Nalesso, Gg.nalesso@surrey.ac.ukUNSPECIFIED
Ruether, WUNSPECIFIEDUNSPECIFIED
Rutsch, FUNSPECIFIEDUNSPECIFIED
Dell'Accio, FUNSPECIFIEDUNSPECIFIED
Pap, TUNSPECIFIEDUNSPECIFIED
Date : 17 April 2012
Identification Number : https://doi.org/10.1136/annrheumdis-2011-200892
Copyright Disclaimer : © 2012 BMJ Publishing Group
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:48
Last Modified : 18 May 2017 12:44
URI: http://epubs.surrey.ac.uk/id/eprint/829284

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