論文

査読有り
2010年1月

Role of the Low-Density Lipoprotein Receptor-Related Protein-1 in Regulation of Chondrocyte Differentiation

JOURNAL OF CELLULAR PHYSIOLOGY
  • Kazumi Kawata
  • ,
  • Satoshi Kubota
  • ,
  • Takanori Eguchi
  • ,
  • Norifumi H. Moritani
  • ,
  • Tsuyoshi Shimo
  • ,
  • Seiji Kondo
  • ,
  • Takashi Nishida
  • ,
  • Shogo Minagi
  • ,
  • Masaharu Takigawa

222
1
開始ページ
138
終了ページ
148
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/jcp.21930
出版者・発行元
WILEY-LISS

The low-density lipoprotein receptor-related protein 1 (LRP1) is known as an endocytic and signal transmission receptor. We formerly reported the gene expression and the localization of LRP1 in cartilage tissue and chondrocytes, but its roles in the differentiation of chondrocytes remained to be investigated. Here, in order to address this issue, we employed RNAi strategy to knockdown Irpl in chondrocytic cells and obtained findings indicating a critical role therein. As a result of IrpI knockdown, aggrecan and col2a1 mRNA levels were decreased. However, that of col10a1 or mmp13 mRNA was rather increased. Under this condition, we performed a promoter assay for Axing, which is known to be induced by activation of the WNT/beta-catenin (beta cat) signaling pathway. Thereby, we found that Axing promoter activity was enhanced in the Irpl knockdown cells. Furthermore, when the WNT/beta-catenin pathway was activated in chondrocytic cells by WNT3a or SB216763, which inhibits the phosphorylation of GSK3 beta, the mRNA levels of aggrecan and col2a1 were decreased, whereas that of mmp13 was increased. Additionally, the level of phosphorylated protein kinase C (PKC) zeta was also decreased in the Irp1 knockdown cells. When the phosphorylation of PKC zeta was selectively inhibited, aggrecan and col2a1 mRNA levels decreased, whereas the mmp13 mRNA level increased. These data demonstrate that LRP1 exerts remarkable effects to retain the mature phenotype of chondrocytes as a critical mediator of cell signaling. Our findings also indicate that the onset of hypertrophy during endochondral ossification appears to be particularly dependent on the WNT and PKC signaling initiated by LRP1. J. Cell. Physiol. 222: 138-148, 2010. (C) 2009 Wiley-Liss, Inc.

Web of Science ® 被引用回数 : 23

リンク情報
DOI
https://doi.org/10.1002/jcp.21930
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19795391
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000272528300018&DestApp=WOS_CPL

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