Lysophosphatidic acid stimulates cell proliferation in rat chondrocytes.
Rat primary chondrocytes express the lysophosphatidic acid (LPA) receptor, LPA1, LPA3, but not LPA2. When chondrocytes were stimulated with LPA, phospholipase C-mediated cytosolic calcium increase was dramatically induced. LPA also stimulated two kinds of mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK) and p38 kinase in chondrocytes. In terms of the LPA-mediated functional modulation of chondrocytes, LPA stimulated cellular proliferation. We examined the signaling pathways involved in LPA-mediated cellular proliferation. LPA-induced chondrocyte proliferation was almost completely blocked by 2'-amino-3'-methoxyflavone (PD98059) but not by 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), suggesting that ERK activity is essentially required for the process. Pertussis toxin almost completely inhibited the LPA-induced cellular proliferation and ERK activation, indicating the role of G(i/o) protein(s) in the processes. This study demonstrates the physiological role of LPA on the modulation of rat primary chondrocyte proliferation, and the crucial role played by ERK in the process.
Kim
Mi-Kyoung
MK
Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Lee
Ha-Young
HY
Park
Kyoung Sun
KS
Shin
Eun Ha
EH
Jo
Seong Ho
SH
Yun
Jeanho
J
Lee
Sung Won
SW
Yoo
Young Hyun
YH
Lee
Yun-Sik
YS
Baek
Suk-Hwan
SH
Bae
Yoe-Sik
YS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D049368:Receptors, Lysophosphatidic Acid / Q000032:analysis; D010738:Type C Phospholipases / Q000502:physiology
D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; C032881:lysophosphatidic acid; D002118:Calcium