Volume 7 Supplement 1

25th European Workshop for Rheumatology Research

Open Access

Heme oxygenase 1 regulates osteoclastogenesis

  • J Zwerina1,
  • S Hayer1,
  • K Redlich1,
  • I Radda1,
  • O Hoffmann2,
  • JS Smolen1 and
  • G Schett1
Arthritis Research & Therapy20057(Suppl 1):P40

DOI: 10.1186/ar1561

Received: 11 January 2005

Published: 17 February 2005

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).

Authors’ Affiliations

Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna
Institute for Pharmacy, University of Vienna


© BioMed Central Ltd 2005