ScIentIfIc REPORTS | 7: 16701 | DOI:10.1038/s41598-017-16902-4
acyltransferase 4 is involved in
chondrogenic dierentiation of
, Hisako Hikiji
, Wataru Ariyoshi
, Tomomi Hashidate-Yoshida
, Takao Shimizu
, Toshinori Okinaga
, Yuji Seta
, Kazuhiro Tominaga
Glycerophospholipids have important structural and functional roles in cells and are the main
components of cellular membranes. Glycerophospholipids are formed via the de novo pathway
(Kennedy pathway) and are subsequently matured in the remodeling pathway (Lands’ cycle). Lands’
cycle consists of two steps: deacylation of phospholipids by phospholipases A
of lysophospholipids by lysophospholipid acyltransferases (LPLATs). LPLATs play key roles in the
maturation and maintenance of the fatty acid composition of biomembranes, and cell dierentiation.
We examined whether LPLATs are involved in chondrogenic dierentiation of ATDC5 cells, which can
dierentiate into chondrocytes. Lysophosphatidylcholine acyltransferase 4 (LPCAT4) mRNA expression
and LPCAT enzymatic activity towards 18:1-, 18:2-, 20:4-, and 22:6-CoA increased in the late stage of
chondrogenic dierentiation, when mineralization occurred. LPCAT4 knockdown decreased mRNA
and protein levels of chondrogenic markers as well as Alcian blue staining intensity and alkaline
phosphatase activity in ATDC5 cells. These results suggest that LPCAT4 plays important roles during the
transition of chondrocytes into hypertrophic chondrocytes and/or a mineralized phenotype.
Glycerophospholipids have major functional and structural roles in cellular membranes. ey provide precursors
of lipid mediators, such as prostaglandins, leukotrienes, platelet-activating factor, and lysophospholipids
are dierent classes of glycerophospholipids: phosphatidic acid, phosphatidylcholine (PC), phosphatidyletha-
nolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, and cardiolipin
. e fatty acids in
glycerophospholipids can widely vary between cell types and tissues. PC is the most abundant glycerophospho-
lipid in mammalian cell membranes
. It plays a role in balancing the proportion of bilayer lipids that determine
membrane intrinsic curvature
Glycerophospholipids are formed from glycerol-3-phosphate in the de novo pathway (Kennedy pathway
and are subsequently remodeled by deacylation and reacylation (Lands’ cycle
). In the Land’s cycle, the concerted
actions of phospholipases A
and lysophospholipid acyltransferases (LPLATs) modify the fatty acid composition
. LPLATs, which are important for maintaining an appropriate fatty acid composition
of glycerophospholipids in cells, are widely distributed in tissues and show varying substrate preferences for
acyl-CoAs and lysophospholipids
. LPLATs have been identied in the membrane-bound O-acyltransferase
(MBOAT) and 1-acyl-glycerol-3-phosphate O-acyltransferase families
Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University,
Kitakyushu, Fukuoka, 803-8580, Japan.
Division of Oral and Maxillofacial Surgery, Department of Science of
Physical Functions, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
School of Oral Health
Sciences, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
Department of Lipid Signaling,
Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, 162-8655, Japan.
for Medical Research and Development-Core Research for Evolutional Medical Science and Technology (AMED-
CREST), AMED, Chiyoda-ku, Tokyo, 100-0004, Japan.
Department of Lipidomics, Graduate School of Medicine, The
University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Division of Anatomy, Department of Health Improvement,
Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan. Correspondence and requests for materials should
be addressed to H.H. (email: firstname.lastname@example.org)
Received: 25 February 2016
Accepted: 20 November 2017
Published: xx xx xxxx