PT  - JOURNAL ARTICLE
AU  - J Bertrand
AU  - Y Nitschke
AU  - M Fuerst
AU  - S Hermann
AU  - M Schäfers
AU  - J Sherwood
AU  - G Nalesso
AU  - W Ruether
AU  - F Rutsch
AU  - F Dell'Accio
AU  - T Pap
TI  - Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice
AID  - 10.1136/annrheumdis-2011-200892
DP  - 2012 Jul 01
TA  - Annals of the Rheumatic Diseases
PG  - 1249--1253
VI  - 71
IP  - 7
4099  - http://ard.bmj.com/content/71/7/1249.short
4100  - http://ard.bmj.com/content/71/7/1249.full
SO  - Ann Rheum Dis2012 Jul 01; 71
AB  - 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.