論文

査読有り
2012年6月

Role of LRP1 in transport of CCN2 protein in chondrocytes

JOURNAL OF CELL SCIENCE
  • Kazumi Kawata
  • ,
  • Satoshi Kubota
  • ,
  • Takanori Eguchi
  • ,
  • Eriko Aoyama
  • ,
  • Norifumi H. Moritani
  • ,
  • Seiji Kondo
  • ,
  • Takashi Nishida
  • ,
  • Masaharu Takigawa

125
12
開始ページ
2965
終了ページ
2972
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1242/jcs.101956
出版者・発行元
COMPANY OF BIOLOGISTS LTD

Low-density lipoprotein receptor-related protein 1 (LRP1) is known to be a receptor for signal transmission and endocytosis. We have previously reported that LRP1 regulates WNT-beta-catenin and protein kinase C signaling in chondrocytes, represses the hypertrophy of chondrocytes during endochondral ossification and that LRP1 is colocalized with a ligand, CCN family member 2 (CCN2; also known as connective tissue growth factor, CTGF), which conducts endochondral ossification, in chondrocytes. However, the role of LRP1 in the endocytic transport of CCN2 in chondrocytes is not yet understood. In the present study, we investigated the interaction between LRP1 and CCN2 during endocytic trafficking. Small interfering RNA (siRNA)-mediated knockdown of LRP1 in chondrocytic HCS-2/8 cells showed that the amount of exogenous CCN2 binding and/or incorporation was decreased in the LRP1 downregulated cells. Importantly, we observed that CCN2 internalization in chondrocytes was dependent on clathrin, and internalizated CCN2 was colocalized with an early or recycling endosome marker. Transcytosis of CCN2 through HCS-2/8 cells was confirmed by performing experiments with a trans-well apparatus, and the amount of transcytosed CCN2 was decreased by an LRP1 antagonist. These findings rule out possible leakage and confirm the crucial involvement of LRP1 during experimental transcytosis. Moreover, under hypoxic conditions that mimic the cartilaginous microenvironment, the level of LRP1 and the amount of transcytosed CCN2 increased, and these increases were neutralized by treatment with the LRP1 antagonist. The distribution of LRP1 and its antagonist in the growth plate in vivo was consistent with that of CCN2 in this tissue, which is produced by and transported by LRP1 from the chondrocytes in the prehypertrophic layer. These findings suggest that LRP1 mediates the transcytosis of CCN2, which might be a crucial event that determines the distribution of CCN2 in cartilage.

Web of Science ® 被引用回数 : 33

リンク情報
DOI
https://doi.org/10.1242/jcs.101956
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22454511
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000307767100019&DestApp=WOS_CPL

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