| Involvement of aquaporin 9 in osteoclast differentiation. | |
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MedLine Citation:
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PMID: 16698796 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aquaporins (water channels) selectively enhance water permeability of membranes. Since osteoclast differentiation includes a dramatic increase in cell volume, we hypothesize that aquaporin(s) is/are critical for the formation of the multinucleated osteoclast from its mononuclear precursor. Our studies employ two cell models, bone marrow macrophages (BMMs) and the murine macrophage-like cell line, RAW264.7, as osteoclast precursors. Receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) and macrophage-colony-stimulating factor or RANKL alone were used to induce osteoclast differentiation in BMMs or RAW264.7 cells, respectively. We first used qualitative reverse transcription (RT)-PCR to examine which of the aquaporins are expressed in osteoclasts and in their precursor cells. Out of the 10 aquaporins examined, only aquaporin 9 (AQP9) was expressed in osteoclast-lineage cells. AQP9 has unique aqueous pore properties mediating the passage of a wide variety of non-charged solutes in addition to water. Western analyses using specific antibodies revealed a higher AQP9 level in RANKL-treated than in untreated cells. Quantitative real-time RT-PCR analyses also demonstrated higher AQP9 mRNA levels in RANKL-treated cells. Finally, we examined the effect of phloretin, an AQP9 inhibitor, on RANKL-induced osteoclast differentiation. Cells were incubated with RANKL for 5 days, and phloretin was added for the last 2 days, when most fusion occurs. A dramatic reduction in osteoclast size and in the number of nuclei per osteoclast was observed in cultures containing phloretin. The inhibitor did not have a significant effect on the number and size of mononuclear phagocytes in cultures not treated with RANKL. Our results suggest a role for AQP9 in osteoclast differentiation, specifically in the fusion process. |
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Authors:
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Refael Aharon; Zvi Bar-Shavit |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-05-12 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 281 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-10 Completed Date: 2006-08-21 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 19305-9 Citation Subset: IM |
Affiliation:
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Humphrey Center for Experimental Medicine and Cancer Research, The Hebrew University Faculty of Medicine, Jerusalem 91120, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aquaporins / metabolism, physiology* Bone Marrow Cells / cytology Carrier Proteins / metabolism Cell Differentiation Cell Line Cells, Cultured Macrophages / metabolism Membrane Glycoproteins / metabolism Mice Mice, Inbred BALB C Osteoclasts / metabolism Phagocytes / metabolism Phloretin / pharmacology RANK Ligand Receptor Activator of Nuclear Factor-kappa B |
| Grant Support | |
ID/Acronym/Agency:
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P01 AR48818/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aqp9 protein, mouse; 0/Aquaporins; 0/Carrier Proteins; 0/Membrane Glycoproteins; 0/RANK Ligand; 0/Receptor Activator of Nuclear Factor-kappa B; 0/Tnfrsf11a protein, mouse; 0/Tnfsf11 protein, mouse; 60-82-2/Phloretin |
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