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This article is part of the supplement: 25th European Workshop for Rheumatology Research

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Heme oxygenase 1 regulates osteoclastogenesis

J Zwerina1, S Hayer1, K Redlich1, I Radda1, O Hoffmann2, JS Smolen1 and G Schett1

Author Affiliations

1 Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Austria

2 Institute for Pharmacy, University of Vienna, Austria

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Arthritis Research & Therapy 2005, 7(Suppl 1):P40  doi:10.1186/ar1561

The electronic version of this article is the complete one and can be found online at:

Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Poster presentation

Heme oxygenase 1 (HO-1) plays an important role in vascular disease, transplantation and inflammation. In animal models of acute and chronic inflammation, induction of HO-1 has anti-inflammatory and cytoprotective properties. Since inflammation is an important trigger of osteoclastogenesis, we hypothesized that HO-1 might play a role in osteoclastogenesis.

When HO-1 was induced by hemin in vitro, a significant dose-dependent inhibitory effect on osteoclastogenesis was observed. Hemin primarily inhibited differentiation of mononuclear osteoclast precusors to osteoclasts. These effects were based on a downregulation of the expression of c-fms and RANK, the receptors for monocyte-colony stimulating factor and RANKL, whereas MAP kinase, NF-κB or Akt signalling were not affected. In vivo, HO-1 induction prevented endotoxin-induced calvarial bone resorption. Furthermore, assessment of synovial tissue from rheumatoid arthritis (RA) patients showed expression of HO-1 in monocytes and fibroblasts, whereas osteoclasts were rarely HO-1 positive. To further assess the role of HO-1 activity in RA patients, we correlated the presence of local bone erosions with serum bilirubin levels. We observed significant higher bilirubin levels in non-erosive than in erosive RA patients. Thus, an increase of HO-1 expression is anti-osteoclastogenic in vitro and might protect from increased bone resorption in vivo.


This study was supported by the START price of the Austrian Science Fund (GS).