1. Inhibition of osteoclastogenesis by prolyl hydroxylase inhibitor dimethyloxallyl glycine
- Author
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Leocadia M. Mosquea, Seng H. Cheng, Nelson S. Yew, Antonius Song, Canwen Jiang, Adam J. Belanger, Andrew Leger, and Allison Altobelli
- 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 - 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.
- Published
- 2009