ATX-LPA 1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation

Tatsuji Nishioka, Naoaki Arima, Kuniyuki Kano, Kotaro Hama, Eriko Itai, Hiroshi Yukiura, Ryoji Kise, Asuka Inoue, Seok Hyung Kim, Lilianna Solnica-Krezel, Wouter H. Moolenaar, Jerold Chun, Junken Aoki

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

The lipid mediator lysophosphatidic acid (LPA) signals via six distinct G protein-coupled receptors to mediate both unique and overlapping biological effects, including cell migration, proliferation and survival. LPA is produced extracellularly by autotaxin (ATX), a secreted lysophospholipase D, from lysophosphatidylcholine. ATX-LPA receptor signaling is essential for normal development and implicated in various (patho)physiological processes, but underlying mechanisms remain incompletely understood. Through gene targeting approaches in zebrafish and mice, we show here that loss of ATX-LPA 1 signaling leads to disorganization of chondrocytes, causing severe defects in cartilage formation. Mechanistically, ATX-LPA 1 signaling acts by promoting S-phase entry and cell proliferation of chondrocytes both in vitro and in vivo, at least in part through β1-integrin translocation leading to fibronectin assembly and further extracellular matrix deposition; this in turn promotes chondrocyte-matrix adhesion and cell proliferation. Thus, the ATX-LPA 1 axis is a key regulator of cartilage formation.

Original languageEnglish
Article number23433
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Mar 23

ASJC Scopus subject areas

  • General

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