Lysophosphatidic acid stimulates cell proliferation in rat chondrocytes

Rat primary chondrocytes express the lysophosphatidic acid (LPA) receptor, LPA 1, LPA 3, but not LPA 2. 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)1 H-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.