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Inhibition of osteoclastogenesis by prolyl hydroxylase inhibitor dimethyloxallyl glycine
- Source :
- Journal of bone and mineral metabolism. 28(5)
- Publication Year :
- 2009
-
Abstract
- Studies examining the effects of hypoxia upon osteoclast biology have consistently revealed a stimulatory effect; both osteoclast differentiation and resorption activity have been shown to be enhanced in the presence of hypoxia. In the present study we examined the effects of the hypoxia mimetics dimethyloxallyl glycine (DMOG) and desferrioxamine (DFO) upon osteoclastogenesis. In contrast to hypoxia, our studies revealed a dose-dependent inhibition of osteoclast formation from macrophages treated with DMOG and DFO. Moreover, expression of a constitutively active form of hypoxia-inducible factor 1alpha (HIF-1alpha) did not enhance osteoclastogenesis and actually attenuated the differentiation process. DMOG did not affect cell viability or receptor activator of nuclear factor kappaB ligand (RANKL)-dependent phosphorylation of mitogen-activated protein (MAP) kinases. However, RANKL-dependent transcription of tartrate-resistant acid phosphatase (TRAP) was reduced in the presence of DMOG. Additionally, DMOG promoted transcription of the pro-apoptotic mediator B-Nip3. These studies suggest that a hypoxia-responsive factor other than HIF-1alpha is necessary for enhancing the formation of osteoclasts in hypoxic settings.
- Subjects :
- Macrophage colony-stimulating factor
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Glycine
Procollagen-Proline Dioxygenase
Osteoclasts
Siderophores
Deferoxamine
Cell Line
Rats, Sprague-Dawley
Mice
Endocrinology
Osteoclast
Internal medicine
medicine
Animals
Orthopedics and Sports Medicine
Hypoxia
biology
Kinase
Activator (genetics)
Macrophage Colony-Stimulating Factor
RANK Ligand
Cell Differentiation
General Medicine
Hypoxia-Inducible Factor 1, alpha Subunit
Cell biology
Rats
medicine.anatomical_structure
Gene Expression Regulation
RANKL
biology.protein
Phosphorylation
Female
Procollagen-proline dioxygenase
Mitogen-Activated Protein Kinases
Subjects
Details
- ISSN :
- 14355604
- Volume :
- 28
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of bone and mineral metabolism
- Accession number :
- edsair.doi.dedup.....5f0847334d79c71b28935644fdd0a374