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Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts.

Authors: Lin, TH  Tang, CH  Hung, SY  Liu, SH  Lin, YM  Fu, WM  Yang, RS 
Citation: Lin TH, etal., J Cell Physiol. 2010 Mar;222(3):757-68.
Pubmed: (View Article at PubMed) PMID:20020468
DOI: Full-text: DOI:10.1002/jcp.22008

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 H(2)O(2), lipopolysaccharide and inflammatory cytokines such as TNF-alpha and IL-1beta in osteoblasts and also in STZ-induced diabetic mice. In addition, endogenous PPARgamma ligand, 15-deoxy-Delta(12,14)-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.


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CRRD Object Information
CRRD ID: 2316141
Created: 2010-01-27
Species: All species
Last Modified: 2010-01-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.