Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity
Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity
复制标题
DOI：
10.1002/jcp.10270
复制
发表时间：
2003-07-01
影响因子：
5.6
通讯作者：
Chihara, K
中科院分区：
文献类型：
--
作者：
Kanatan, M;Sugimoto, T;Chihara, K
尽管培养液中高浓度的无机磷直接抑制新的破骨细胞的生成，也抑制成熟破骨细胞的骨吸收，但其确切的机制和生理作用尚不清楚。本研究就是针对这些问题展开的。增加胞外PI浓度(2.5-4 mM)可抑制1，25-二羟基维生素D-3[1，25(OH)(2)D-3]或甲状旁腺激素(PTH)-(1-34)诱导的破骨细胞样细胞的形成。[PI](E)(2.5-4 mM)浓度的增加可依赖地抑制1，25(OH)(2)D-3-、PTH-(1-34)-或核因子-kappaB受体激活剂(RANKL)和巨噬细胞集落刺激因子(M-CSF)诱导的破骨细胞样细胞的形成。[PI](E)(2.5~4 mM)浓度依赖性地刺激骨保护素(OPG)mRNA的表达，并增强PTH-(1-34)或1，25(OH)(2)D-3抑制的OPG mRNA的表达，但不影响RANKL的表达。[PI](E)浓度的增加(2.5-4 mM)可依赖地抑制兔破骨细胞的骨吸收活性。[PI](E)(4 MM)浓度升高可诱导体外培养的兔破骨细胞发生凋亡，但对破骨细胞前体细胞和在RANKL和M-CSF存在下可分化为破骨细胞的小鼠巨噬细胞系C7细胞无明显影响。这些结果表明，[PI](E)的增加通过上调OPG的表达和直接作用于破骨细胞前体细胞来抑制破骨细胞的分化。研究还表明，[PI](E)的增加至少部分地通过直接诱导破骨细胞的凋亡来抑制破骨活性。(C)2003年Wiley-Liss，Inc.
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. (C) 2003 Wiley-Liss, Inc.