論文

査読有り
2013年7月

CCN3 Protein Participates in Bone Regeneration as an Inhibitory Factor

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Yuki Matsushita
  • ,
  • Kei Sakamoto
  • ,
  • Yoshihiro Tamamura
  • ,
  • Yasuaki Shibata
  • ,
  • Tokutaro Minamizato
  • ,
  • Tasuku Kihara
  • ,
  • Masako Ito
  • ,
  • Ken-ichi Katsube
  • ,
  • Shuichi Hiraoka
  • ,
  • Haruhiko Koseki
  • ,
  • Kiyoshi Harada
  • ,
  • Akira Yamaguchi

288
27
開始ページ
19973
終了ページ
19985
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M113.454652
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

CCN3, a member of the CCN protein family, inhibits osteoblast differentiation in vitro. However, the role of CCN3 in bone regeneration has not been well elucidated. In this study, we investigated the role of CCN3 in bone regeneration. We identified the Ccn3 gene by microarray analysis as a highly expressed gene at the early phase of bone regeneration in a mouse bone regeneration model. We confirmed the up-regulation of Ccn3 at the early phase of bone regeneration by RT-PCR, Western blot, and immunofluorescence analyses. Ccn3 transgenic mice, in which Ccn3 expression was driven by 2.3-kb Col1a1 promoter, showed osteopenia compared with wild-type mice, but Ccn3 knock-out mice showed no skeletal changes compared with wild-type mice. We analyzed the bone regeneration process in Ccn3 transgenic mice and Ccn3 knock-out mice by microcomputed tomography and histological analyses. Bone regeneration in Ccn3 knock-out mice was accelerated compared with that in wild-type mice. The mRNA expression levels of osteoblast-related genes (Runx2, Sp7, Col1a1, Alpl, and Bglap) in Ccn3 knock-out mice were up-regulated earlier than those in wildtype mice, as demonstrated by RT-PCR. Bone regeneration in Ccn3 transgenic mice showed no significant changes compared with that in wild-type mice. Phosphorylation of Smad1/5 was highly up-regulated at bone regeneration sites in Ccn3 KO mice compared with wild-type mice. These results indicate that CCN3 is up-regulated in the early phase of bone regeneration and acts as a negative regulator for bone regeneration. This study may contribute to the development of new strategies for bone regeneration therapy.

Web of Science ® 被引用回数 : 27

リンク情報
DOI
https://doi.org/10.1074/jbc.M113.454652
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23653360
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000321515800062&DestApp=WOS_CPL

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