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Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity.
J Cell Physiol. 2003 Jul; 196(1):180-9.JC

Abstract

Although high inorganic phosphate (Pi) concentration in culture media directly inhibits generation of new osteoclasts and also inhibits bone resorption by mature osteoclasts, its precise mechanism and the physiological role have not been elucidated. The present study was performed to investigate these issues. Increase in extracellular Pi concentration ([Pi](e)) (2.5-4 mM) concentration dependently inhibited 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] or parathyroid hormone (PTH)-(1-34)-induced osteoclast-like cell formation from unfractionated bone cells in the presence of stromal cells. Increase in [Pi](e) (2.5-4 mM) concentration dependently inhibited 1,25(OH)(2)D(3)-, PTH-(1-34)-, or receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF)-induced osteoclast-like cell formation from hemopoietic blast cells in the absence of stromal cells. Increase in [Pi](e) (2.5-4 mM) dose dependently stimulated the expression of osteoprotegerin (OPG) mRNA and increased the expression of OPG mRNA suppressed by PTH-(1-34) or 1,25(OH)(2)D(3) in unfractionated bone cells, while it did not affect RANKL mRNA. Increase in [Pi](e) (2.5-4 mM) concentration dependently inhibited the bone-resorbing activity of isolated rabbit osteoclasts. Increase in [Pi](e) (4 mM) induced the apoptosis of isolated rabbit osteoclasts while it did not affect the apoptosis of osteoclast precursor cells and mouse macrophage-like cell line C7 cells that can differentiate into osteoclasts in the presence of RANKL and M-CSF. These results indicate that increase in [Pi](e) inhibits osteoclast differentiation both by up-regulating OPG expression and by direct action on osteoclast precursor cells. It is also indicated that increase in [Pi](e) inhibits osteoclastic activity at least in part by the direct induction of apoptosis of osteoclasts.

Authors+Show Affiliations

Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12767054

Citation

Kanatani, Masanori, et al. "Effect of High Phosphate Concentration On Osteoclast Differentiation as Well as Bone-resorbing Activity." Journal of Cellular Physiology, vol. 196, no. 1, 2003, pp. 180-9.
Kanatani M, Sugimoto T, Kano J, et al. Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity. J Cell Physiol. 2003;196(1):180-9.
Kanatani, M., Sugimoto, T., Kano, J., Kanzawa, M., & Chihara, K. (2003). Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity. Journal of Cellular Physiology, 196(1), 180-9.
Kanatani M, et al. Effect of High Phosphate Concentration On Osteoclast Differentiation as Well as Bone-resorbing Activity. J Cell Physiol. 2003;196(1):180-9. PubMed PMID: 12767054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity. AU - Kanatani,Masanori, AU - Sugimoto,Toshitsugu, AU - Kano,Junichi, AU - Kanzawa,Michiko, AU - Chihara,Kazuo, PY - 2003/5/27/pubmed PY - 2003/7/17/medline PY - 2003/5/27/entrez SP - 180 EP - 9 JF - Journal of cellular physiology JO - J Cell Physiol VL - 196 IS - 1 N2 - Although high inorganic phosphate (Pi) concentration in culture media directly inhibits generation of new osteoclasts and also inhibits bone resorption by mature osteoclasts, its precise mechanism and the physiological role have not been elucidated. The present study was performed to investigate these issues. Increase in extracellular Pi concentration ([Pi](e)) (2.5-4 mM) concentration dependently inhibited 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] or parathyroid hormone (PTH)-(1-34)-induced osteoclast-like cell formation from unfractionated bone cells in the presence of stromal cells. Increase in [Pi](e) (2.5-4 mM) concentration dependently inhibited 1,25(OH)(2)D(3)-, PTH-(1-34)-, or receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF)-induced osteoclast-like cell formation from hemopoietic blast cells in the absence of stromal cells. Increase in [Pi](e) (2.5-4 mM) dose dependently stimulated the expression of osteoprotegerin (OPG) mRNA and increased the expression of OPG mRNA suppressed by PTH-(1-34) or 1,25(OH)(2)D(3) in unfractionated bone cells, while it did not affect RANKL mRNA. Increase in [Pi](e) (2.5-4 mM) concentration dependently inhibited the bone-resorbing activity of isolated rabbit osteoclasts. Increase in [Pi](e) (4 mM) induced the apoptosis of isolated rabbit osteoclasts while it did not affect the apoptosis of osteoclast precursor cells and mouse macrophage-like cell line C7 cells that can differentiate into osteoclasts in the presence of RANKL and M-CSF. These results indicate that increase in [Pi](e) inhibits osteoclast differentiation both by up-regulating OPG expression and by direct action on osteoclast precursor cells. It is also indicated that increase in [Pi](e) inhibits osteoclastic activity at least in part by the direct induction of apoptosis of osteoclasts. SN - 0021-9541 UR - https://www.unboundmedicine.com/medline/citation/12767054/Effect_of_high_phosphate_concentration_on_osteoclast_differentiation_as_well_as_bone_resorbing_activity_ L2 - https://doi.org/10.1002/jcp.10270 DB - PRIME DP - Unbound Medicine ER -