FGFR3 down-regulates PTH/PTHrP receptor gene expression by mediating JAK/STAT signaling in chondrocytic cell line

Li, Minqi; Seki, Yukie; Freitas, Paulo H. L. et al.

Journal of Electron Microscopy, 2010, 59(3), 227-236

Permalink : https://hdl.handle.net/2115/44953

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アクセス権
open access
URI
https://hdl.handle.net/2115/44953
タイトル
FGFR3 down-regulates PTH/PTHrP receptor gene expression by mediating JAK/STAT signaling in chondrocytic cell line
著者
Li, Minqi ; Seki, Yukie ; Freitas, Paulo H. L. ; Nagata, Masaki ; Kojima, Taku ; Sultana, Sara ; Ubaidus, Sobhan ; Maeda, Takeyasu ; Shimomura, Junko ; Henderson, Janet E. ; Tamura, Masato ; Oda, Kimimitsu ; Liu, Zhusheng ; Guo, Ying ; Suzuki, Reiko ; Yamamoto, Tsuneyuki ; Takagi, Ritsuo ; Amizuka, Norio
著者名
Li, Minqi
著者名
Seki, Yukie
著者名
Freitas, Paulo H. L.
著者名
Nagata, Masaki
著者名
Kojima, Taku
著者名
Sultana, Sara
著者名
Ubaidus, Sobhan
著者名
Maeda, Takeyasu
著者名
Shimomura, Junko
著者名
Henderson, Janet E.
著者名
Tamura, Masato
著者名
Oda, Kimimitsu
著者名
Liu, Zhusheng
著者名
Guo, Ying
著者名
Suzuki, Reiko
著者名
Yamamoto, Tsuneyuki
著者名
Takagi, Ritsuo
著者名
Amizuka, Norio
言語
英語
キーワード
FGFR3
PTH/PTHrP receptor
chondrocyte
PTHrP
cell proliferation
発行日
2010-06
出版者
Oxford University Press
収録物名
Journal of Electron Microscopy
巻(号)
59(3)
ページ
227-236
抄録
The signaling axis comprised by the parathyroid hormone (PTH)-related peptide (PTHrP), the PTH/PTHrP receptor and the fibroblast growth factor receptor 3 (FGFR3) plays a central role in chondrocyte proliferation. The Indian hedgehog (IHH) gene is normally expressed in early hypertrophic chondrocytes, and its negative feedback loop was shown to regulate PTH/PTHrP receptor signaling. In this study, we examined the regulation of PTH/PTHrP receptor gene expression in a FGFR3-transfected chondrocytic cell line, CFK2. Expression of IHH could not be verified on these cells, with consequent absence of hypertrophic differentiation. Also, expression of the PTH/PTHrP receptor (75% reduction of total mRNA) and the PTHrP (50% reduction) genes was reduced in CFK2 cells transfected with FGFR3 cDNA. Interestingly, we verified significant reduction in cell growth and increased apoptosis in the transfected cells. STAT1 was detected in the nuclei of the CFK2 cells transfected with FGFR3 cDNA, indicating predominance of the JAK/STAT signaling pathway. The reduction in PTH/PTHrP receptor gene in CFK2 cells over-expressing FGFR3 was partially blocked by treatment with an inhibitor of JAK3 (WHI-P131), but not with an inhibitor of MAPK (SB203580) or JAK2 (AG490). Altogether, these findings suggest that FGFR3 down-regulates PTH/PTHrP receptor gene expression via the JAK/STAT signaling in chondrocytic cells.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
権利情報
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Electron Microscopy following peer review. The definitive publisher-authenticated version Journal of Electron Microscopy 2010 59(3):227-236 is available online at: http://jmicro.oxfordjournals.org/cgi/content/abstract/59/3/227
PISSN
0022-0744
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1093/jmicro/dfq002