Roles of lysophosphatidic acid and the Rho-associated kinase pathway in the migration of dental pulp cells.
During the dental pulp repair process, dental pulp cells (DPCs) migrate to the site of injury and differentiate into odontoblasts or odontoblast-like cells. Although migration of DPCs is an important reparative process, the underlying mechanism remains unknown. The objective of this study was to determine the roles of lysophosphatidic acid (LPA) and the Rho-associated kinase (ROCK) pathway in the migration and morphology of dental pulp cells and alpha smooth muscle actin expression in vitro. We demonstrated that both LPA and ROCK inhibition enhanced cell motility and that their combined effects significantly increased migration rate. LPA induced fine cytoskeleton assembly and increased the level of alpha smooth muscle actin (alpha-SMA). ROCK inhibition by Y-27632 and ROCK-(1+2) small interfering RNA (siRNA) resulted in less actin cytoskeleton formation, a lower alpha-SMA level, a star-like cellular morphology and membrane ruffling. LPA and ROCK inhibition induced activation of another Rho GTPase, Rac, which may explain how LPA and ROCK inhibition increases cellmigration and lamellipodium formation.
Cheng
Ran
R
The State Key Laboratory of Oral Diseases, Sichuan University, 14# 3rd section, Renmin South Road, Chengdu 610041, PR China. applecrbb@gmail.com
Cheng
Li
L
Shao
Mei-ying
MY
Yang
Hui
H
Wang
Feng-ming
FM
Hu
Tao
T
Zhou
Xue-dong
XD
D000199:Actins / Q000378:metabolism; D000328:Adult; D000577:Amides / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D011725:Pyridines / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C541116:ACTA2 protein, human; D000199:Actins; D000577:Amides; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D011725:Pyridines; D034741:RNA, Small Interfering; C108830:Y 27632; D054460:rho-Associated Kinases; D020830:rac1 GTP-Binding Protein; C032881:lysophosphatidic acid