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Erschienen in:

01.09.2010 | Original Article

Inhibition of osteoclastogenesis by prolyl hydroxylase inhibitor dimethyloxallyl glycine

verfasst von: Andrew J. Leger, Allison Altobelli, Leocadia M. Mosquea, Adam J. Belanger, Antonius Song, Seng H. Cheng, Canwen Jiang, Nelson S. Yew

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 5/2010

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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 1α (HIF-1α) did not enhance osteoclastogenesis and actually attenuated the differentiation process. DMOG did not affect cell viability or receptor activator of nuclear factor κB 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-1α is necessary for enhancing the formation of osteoclasts in hypoxic settings.

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Titel: Inhibition of osteoclastogenesis by prolyl hydroxylase inhibitor dimethyloxallyl glycine
verfasst von: Andrew J. Leger
Allison Altobelli
Leocadia M. Mosquea
Adam J. Belanger
Antonius Song
Seng H. Cheng
Canwen Jiang
Nelson S. Yew
Publikationsdatum: 01.09.2010
Verlag: Springer Japan
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 5/2010
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-010-0171-6

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