Upregulation of heme oxygenase‐1 inhibits the maturation and mineralization of osteoblasts
- 17 December 2009
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 222 (3), 757-768
- https://doi.org/10.1002/jcp.22008
Abstract
Heme‐oxygenase‐1 (HO‐1), an important enzyme involved in vascular disease, transplantation, and inflammation, catalyzes the degradation of heme into carbon monoxide and biliverdin. It has been reported that overexpression of HO‐1 inhibits osteoclastogenesis. However, the effect of HO‐1 on osteoblast differentiation is still not clear. We here used adenoviral vector expressing recombinant human HO‐1 and HO‐1 inducer hemin to study the effects of HO‐1 in primary cultured osteoblasts. The results showed that induction of HO‐1 inhibited the maturation of osteoblasts including mineralized bone nodule formation, alkaline phosphatase activity and decreased mRNA expression of several differentiation markers such as alkaline phosphatase, osteocalcin, and RUNX2. Furthermore, downstream products of HO‐1, bilirubin, carbon monoxide, and iron, are involved in the inhibitory action of HO‐1. HO‐1 can be induced by H2O2, lipopolysaccharide and inflammatory cytokines such as TNF‐α and IL‐1β in osteoblasts and also in STZ‐induced diabetic mice. In addition, endogenous PPARγ ligand, 15‐deoxy‐Δ12,14‐prostaglandin‐J2 (15d‐PGJ2) markedly increased both mRNA and protein levels of HO‐1 in osteoblasts via PI3K‐Akt and MAPK pathways. Blockade of HO activity by ZnPP IX antagonized the inhibitory action on osteocalcin expression by hemin and 15d‐PGJ2. Our results indicate that upregulation of HO‐1 inhibits the maturation of osteoblasts and HO‐1 may be involved in oxidative‐ or inflammation‐induced bone loss. J. Cell. Physiol. 222: 757–768, 2010.Keywords
This publication has 48 references indexed in Scilit:
- Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivoMolecular Cancer, 2009
- PPARγ inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in ratsBone, 2007
- Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activationProceedings of the National Academy of Sciences of the United States of America, 2007
- Skeletal Involution by Age-associated Oxidative Stress and Its Acceleration by Loss of Sex SteroidsJournal of Biological Chemistry, 2007
- TNF-α inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signalingBiochemical and Biophysical Research Communications, 2007
- Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic ApplicationsPhysiological Reviews, 2006
- Experimental cholestatic liver disease through bile-duct ligation in rats results in skeletal fragility and impaired osteoblastogenesisJournal of Hepatology, 2004
- Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κBBlood, 2003
- Osteoclast differentiation and activationNature, 2003
- Bone mineral density at the metaphysis is specifically reduced in STZ-treated diabetic ratsLife Sciences, 1996