Division of Research and Development, Meiji Co., Ltd., Tokyo, 192-0919, Japan.
Sci Rep. 2020 Mar 17;10(1):4864. doi: 10.1038/s41598-020-61858-7.
Excessive phosphorus intake adversely affects bone and mineral metabolism. Estrogen is one of the factors affecting fibroblast growth factor 23 (FGF23), a phosphorus-regulating hormone. However, the interaction between excess phosphorus and estrogen status has not been fully elucidated. This study investigated the involvement of estrogen in the effects of high phosphorus intake on bone metabolism and ectopic calcification in ovariectomized (OVX) rats. The interaction between high phosphorus diet and OVX was not observed in bone mineral density and aortic calcium. In contrast, high phosphorus intake markedly increased renal calcium concentration in sham rats, whereas the effect was attenuated in OVX rats, which was reversed by a selective estrogen-receptor modulator treatment. A strong positive correlation between renal calcium and serum FGF23 was observed. In addition, fibroblast growth factor receptor 1 (FGFR1: a predominant receptor of FGF23) inhibitor treatment partially decreased renal calcium concentrations in rats with high phosphorus intake. In conclusion, the effect of high phosphorus intake on bone metabolism and aortic calcification did not depend on the estrogen status; in contrast, high phosphorus intake synergistically induced nephrocalcinosis in the presence of estrogenic action on the bone. Furthermore, FGF23 was involved in the nephrocalcinosis induced by high phosphorus intake partially through FGFR1 signaling.
过量的磷摄入会对骨骼和矿物质代谢产生不良影响。雌激素是影响成纤维细胞生长因子 23（FGF23）的因素之一，FGF23 是一种调节磷的激素。然而，过量的磷和雌激素状态之间的相互作用尚未完全阐明。本研究探讨了雌激素在高磷摄入对去卵巢（OVX）大鼠骨骼代谢和异位钙化影响中的作用。在骨矿物质密度和主动脉钙中未观察到高磷饮食和 OVX 之间的相互作用。相比之下，高磷摄入显著增加了假手术大鼠的肾脏钙浓度，而在 OVX 大鼠中则减弱了该作用，这种作用可被选择性雌激素受体调节剂治疗逆转。在高磷摄入的大鼠中，肾脏钙与血清 FGF23 之间存在强烈的正相关。此外，FGFR1 抑制剂（FGF23 的主要受体）治疗部分降低了高磷摄入大鼠的肾脏钙浓度。总之，高磷摄入对骨骼代谢和主动脉钙化的影响不依赖于雌激素状态；相反，在对骨骼产生雌激素作用的情况下，高磷摄入协同诱导了肾钙质沉着症。此外，FGF23 通过 FGFR1 信号通路部分参与了高磷摄入诱导的肾钙质沉着症。
