Heme oxygenase 1 regulates osteoclastogenesis
© BioMed Central Ltd 2005
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).