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Involvement of aquaporin 9 in osteoclast differentiation.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2006 Jul 14; Vol. 281 (28), pp. 19305-9. Date of Electronic Publication: 2006 May 12. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Animals
Aquaporins metabolism
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
Aquaporins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 281
- Issue :
- 28
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16698796
- Full Text :
- https://doi.org/10.1074/jbc.M601728200