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Heme oxygenase 1 regulates osteoclastogenesis

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).

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Zwerina, J., Hayer, S., Redlich, K. et al. Heme oxygenase 1 regulates osteoclastogenesis. Arthritis Res Ther 7 (Suppl 1), P40 (2005).

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