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Effect of high phosphate concentration on osteoclast differentiation as well as bone‐resorbing activity
Author(s) -
Kanatani Masanori,
Sugimoto Toshitsugu,
Kano Junichi,
Kanzawa Michiko,
Chihara Kazuo
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10270
Subject(s) - rankl , osteoclast , stromal cell , medicine , bone resorption , endocrinology , chemistry , macrophage colony stimulating factor , osteoprotegerin , extracellular , parathyroid hormone , receptor , microbiology and biotechnology , activator (genetics) , macrophage , biology , biochemistry , calcium , in vitro
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‐κB 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. © 2003 Wiley‐Liss, Inc.