Fluoride Modulates Parathyroid Hormone Secretion in vivo and in vitro.
Fluoride Modulates Parathyroid Hormone Secretion in vivo and in vitro.
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DOI：
10.1159/000438699
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Everett ET
中科院分区：
文献类型：
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作者：
Puranik CP;Ryan KA;Yin Z;Martinez-Mier EA;Preisser JS;Everett ET
研究目的是探讨氟对iPTH分泌的影响。将C3 H（n=18）和B6（n=18）小鼠的甲状腺-甲状旁腺复合物（TPC）在钙优化的培养基中培养。将TPC用0、250或500μM NaF处理24小时，并通过ELISA测定分泌的iPTH。C3 H（n=78）和B6（n=78）小鼠用蒸馏水或氟化物（0.001mg [F-]/g体重）水灌胃一次。在连续的时间点（0.5- 96小时）测定血清iPTH、氟、总钙、磷和镁水平。24小时后，检测TPC、肱骨和肾脏中参与骨-甲状旁腺-肾（BPK）轴矿物质调节的基因表达，如：Pth、Casr、Vdr、Pthlh、Fgf 23、αKlotho、Fgf 1 rc、Tnfs 11、Pth 1 r、Slc 34 a1、Slc 9a 3r 1、Clcn 5和Pdzk 1。在500µM时，在C3 H和B6 TPC中观察到iPTH的体外降低（p<0.001）。在C3 H（p=0.002）和B6（p=0.01）中，血清氟的体内水平在0.5小时达到峰值。在C3 H中，iPTH在24小时降低（p<0.0001），在48小时恢复至基线。在B6中，iPTH在12小时增加（p<0.001），在24小时返回至基线。血清总钙、磷、镁无明显变化。与B6相比，C3 H TPC中Pth、Casr、αKlotho、Fgf 1 rc、Vdr和Pthlh显著上调。结论：氟对两种品系小鼠TPC的影响是相当的。然而，氟化物在体内对iPTH分泌表现出早期应变依赖性效应。这两种菌株表现出参与BPK轴的基因表达的差异，表明在生理处理氟可能的作用。
The study objective was to investigate fluoride’s effects on iPTH secretion. Thryo-parathyroid complexes (TPCs) from C3H (n=18) and B6 (n=18) mice were cultured in Ca2+ optimized medium. TPCs were treated with 0, 250 or 500µM NaF for 24hrs and secreted iPTH assayed by ELISA. C3H (n=78) and B6 (n=78) mice were gavaged once with distilled or with fluoride (0.001mg [F−]/g body weight) water. At serial time points (0.5–96hrs) serum iPTH, fluoride, total calcium, phosphorus and magnesium levels were determined. Expression of genes involved in mineral regulation via bone-parathyroid-kidney (BPK) axis such as: Pth, Casr, Vdr, Pthlh, Fgf23, αKlotho, Fgf1rc, Tnfs11, Pth1r, Slc34a1, Slc9a3r1, Clcn5 and Pdzk1 were determined in TPCs, humerii and kidneys at 24hrs. An in vitro decrease in iPTH was seen in C3H and B6 TPC at 500µM (p<0.001). In vivo levels of serum fluoride peaked at 0.5hr in both C3H (p=0.002) and B6 (p=0.01). In C3H, iPTH decreased at 24hrs (p<0.0001) returning to baseline at 48hrs. In B6, iPTH increased at 12hrs (p<0.001) returning to baseline at 24hrs. Serum total calcium, phosphorus and magnesium did not change significantly. Pth, Casr, αKlotho, Fgf1rc, Vdr and Pthlh were significantly up-regulated in C3H TPC as compared to B6. Conclusions, fluoride’s effects on TPC in vitro were equivalent between the two mouse strains. However, fluoride demonstrated an early strain dependent effect on iPTH secretion in vivo. Both strains demonstrated a differences in the expression of genes involved in BPK axis suggesting a possible role in physiologic handling of fluoride.