caa a22 4500 605463204 CHVBK 20210128100252.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00774-014-0598-2 doi (NATIONALLICENCE)springer-10.1007/s00774-014-0598-2 Interleukin-1-induced acute bone resorption facilitates the secretion of fibroblast growth factor 23 into the circulation [Elektronische Daten] [Miwa Yamazaki, Masanobu Kawai, Kazuaki Miyagawa, Yasuhisa Ohata, Kanako Tachikawa, Saori Kinoshita, Jin Nishino, Keiichi Ozono, Toshimi Michigami] Fibroblast growth factor 23 (FGF23), a central regulator of phosphate and vitamin D metabolism, is mainly produced by osteocytes in bone and exerts its effects on distant organs. Despite its endocrine function, the mechanism controlling serum FGF23 levels is not fully understood. Here we tested the hypothesis that osteoclastic bone resorption may play a role in regulating circulating levels of FGF23, using a mouse model where injections of interleukin (IL)-1β into the subcutaneous tissue over the calvaria induced rapid bone resorption. A significant amount of FGF23 was detected in the extracts from mouse bones, which supports the idea that FGF23 stays in bone for a while after its production. IL-1β-induced bone resorption was associated with elevated serum FGF23 levels, an effect abolished by pre-treatment with pamidronate. Fgf23 expression was not increased in either the calvariae or tibiae of IL-1β-injected mice, which suggests that IL-1β facilitated the entry of FGF23 protein into circulation by accelerating bone resorption rather than increasing its gene expression. The direct effect of IL-1β on bone was confirmed when it increased FGF23 levels in the conditioned media of mouse calvariae in organ culture. Repeated treatment of the cultured calvariae with IL-1β led to a refractory phase, where FGF23 was not mobilized by IL-1β anymore. Consistent with the in vivo results, treatment with IL-1β failed to increase Fgf23 mRNA in isolated primary osteocytes and osteoblasts. These results suggest that FGF23 produced by osteocytes remains in bone, and that rapid bone resorption facilitates its entry into the bloodstream. The Japanese Society for Bone and Mineral Research and Springer Japan, 2014 FGF23 nationallicence IL-1β nationallicence Osteocytes nationallicence Osteoclasts nationallicence Bone resorption nationallicence Yamazaki Miwa Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Kawai Masanobu Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Miyagawa Kazuaki Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Ohata Yasuhisa Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Tachikawa Kanako Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Kinoshita Saori Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Nishino Jin Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Ozono Keiichi Department of Pediatrics, Osaka University Graduate School of Medicine, 565-0871, Suita, Osaka, Japan aut Michigami Toshimi Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut Journal of Bone and Mineral Metabolism Springer Japan 33/3(2015-05-01), 342-354 0914-8779 33:3<342 2015 33 774 https://doi.org/10.1007/s00774-014-0598-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00774-014-0598-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamazaki Miwa Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 700 1- Kawai Masanobu Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 700 1- Miyagawa Kazuaki Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 700 1- Ohata Yasuhisa Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 700 1- Tachikawa Kanako Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 700 1- Kinoshita Saori Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 700 1- Nishino Jin Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 700 1- Ozono Keiichi Department of Pediatrics, Osaka University Graduate School of Medicine, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Michigami Toshimi Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 594-1101, Izumi, Osaka, Japan aut NATIONALLICENCE 773 0- Journal of Bone and Mineral Metabolism Springer Japan 33/3(2015-05-01), 342-354 0914-8779 33:3<342 2015 33 774