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Yamazaki, Yuji*; Tamada, Taro; Kasai, Noriyuki*; Urakawa, Itaru*; Aono, Yukiko*; Hasegewa, Hisashi*; Fujita, Toshiro*; Kuroki, Ryota; Yamashita, Takeyoshi*; Fukumoto, Seiji*; et al.
Journal of Bone and Mineral Research, 23(9), p.1509 - 1518, 2008/09
Times Cited Count:150 Percentile:94.53Fibroblast growth factor (FGF)23 is proposed to play a physiological role in the regulation of phosphate and vitamin D metabolism; deranged circulatory levels of FGF23 cause several diseases with abnormal mineral metabolism. We developed two antibodies (FN1 and FC1) that recognize the N- and C-terminal regions of FGF23, respectively. Both FN1 and FC1 inhibited FGF23 activity in a cell-based Klotho-dependent reporter assay. The present study using neutralizing antibodies confirms that FGF23 is a physiological regulator of phosphate and vitamin D metabolism. Then, we addressed the mechanism of action for these neutralizing antibodies. Structural analysis of the FGF23/FN1-Fab complex revealed that FN1 masked putative FGF receptor-binding sites in the N-terminal domain of FGF23, while biochemical analyses showed that FC1 interfered with the association between FGF23 and Klotho by binding to the C-terminal domain of FGF23. Taken together, our results suggest that the N- and C-terminal domains of FGF23 are responsible for association with cognate FGF receptors and Klotho, respectively, and that these interactions are indispensable for FGF23 activity.
Koarai, Kazuma; Matsueda, Makoto; Fujiwara, Kenso; Ono, Takumi*; Kino, Yasushi*; Oka, Toshitaka; Okutsu, Kenichi*; Takahashi, Atsushi*; Suzuki, Toshihiko*; Shimizu, Yoshinaka*; et al.
no journal, ,
We have investigated incorporation of Sr and Cs in teeth of cattle and otoliths of fish. Specific activity of Sr in the dentin tissue was higher than that in the enamel tissue. The result shows change of Sr incorporation in cattle even within a tooth. Concentrations of stable Sr and Cs were 94 ppm and 3 ppb. Distributions of stable Sr and Cs were uniform in the otolith of fish. If distribution of Sr and Cs in the otolith was measured, change of Sr and Cs incorporation into the fish would be found. These findings suggest that distribution patterns of Sr and Cs in the environment could be estimated from distribution of the radionuclides in the tooth and otolith.