Interleukin-1-induced acute bone resorption facilitates the secretion of fibroblast growth factor 23 into the circulation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-07-05

AUTHORS

Miwa Yamazaki, Masanobu Kawai, Kazuaki Miyagawa, Yasuhisa Ohata, Kanako Tachikawa, Saori Kinoshita, Jin Nishino, Keiichi Ozono, Toshimi Michigami

ABSTRACT

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. More... »

PAGES

342-354

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00774-014-0598-2

DOI

http://dx.doi.org/10.1007/s00774-014-0598-2

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24996526


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42 FGF23 protein
43 IL-1β
44 acute bone resorption
45 amount
46 bloodstream
47 bone
48 bone resorption
49 calvaria
50 calvariae
51 central regulator
52 circulation
53 culture
54 cultured calvariae
55 direct effect
56 distant organs
57 effect
58 elevated serum FGF23 levels
59 endocrine function
60 entry
61 expression
62 extract
63 factor 23
64 fibroblast growth factor 23
65 function
66 gene expression
67 growth factor 23
68 hypothesis
69 idea
70 injection
71 injection of interleukin
72 interleukin
73 levels
74 levels of FGF23
75 mRNA
76 mechanism
77 medium
78 metabolism
79 mice
80 model
81 mouse bone
82 mouse calvariae
83 mouse model
84 organ culture
85 organs
86 osteoblasts
87 osteoclastic bone resorption
88 osteocytes
89 pamidronate
90 phase
91 phosphate
92 primary osteocytes
93 production
94 protein
95 rapid bone resorption
96 refractory phase
97 regulator
98 resorption
99 results
100 role
101 secretion
102 serum FGF23 levels
103 significant amount
104 subcutaneous tissue
105 tibia
106 tissue
107 treatment
108 vitamin D metabolism
109 vivo results
110 while
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