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

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Title: FGFR3 down-regulates PTH/PTHrP receptor gene expression by mediating JAK/STAT signaling in chondrocytic cell line
Authors: Li, Minqi Browse this author
Seki, Yukie Browse this author
Freitas, Paulo H. L. Browse this author
Nagata, Masaki Browse this author
Kojima, Taku Browse this author
Sultana, Sara Browse this author
Ubaidus, Sobhan Browse this author
Maeda, Takeyasu Browse this author
Shimomura, Junko Browse this author
Henderson, Janet E. Browse this author
Tamura, Masato Browse this author
Oda, Kimimitsu Browse this author
Liu, Zhusheng Browse this author
Guo, Ying Browse this author
Suzuki, Reiko Browse this author
Yamamoto, Tsuneyuki Browse this author
Takagi, Ritsuo Browse this author
Amizuka, Norio Browse this author
Keywords: FGFR3
PTH/PTHrP receptor
cell proliferation
Issue Date: Jun-2010
Publisher: Oxford University Press
Journal Title: Journal of Electron Microscopy
Volume: 59
Issue: 3
Start Page: 227
End Page: 236
Publisher DOI: 10.1093/jmicro/dfq002
Abstract: 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.
Rights: 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:
Type: article (author version)
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 網塚 憲生

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