TY - JOUR
T1 - ATX-LPA 1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation
AU - Nishioka, Tatsuji
AU - Arima, Naoaki
AU - Kano, Kuniyuki
AU - Hama, Kotaro
AU - Itai, Eriko
AU - Yukiura, Hiroshi
AU - Kise, Ryoji
AU - Inoue, Asuka
AU - Kim, Seok Hyung
AU - Solnica-Krezel, Lilianna
AU - Moolenaar, Wouter H.
AU - Chun, Jerold
AU - Aoki, Junken
PY - 2016/3/23
Y1 - 2016/3/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84961658161&partnerID=8YFLogxK
U2 - 10.1038/srep23433
DO - 10.1038/srep23433
M3 - Article
C2 - 27005960
AN - SCOPUS:84961658161
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 23433
ER -