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 |
chondrocyte |
PTHrP |
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: http://jmicro.oxfordjournals.org/cgi/content/abstract/59/3/227 |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/44953 |
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)
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