Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
J Bone Miner Metab. 2010 Nov;28(6):659-71. doi: 10.1007/s00774-010-0184-1. Epub 2010 May 11.
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophospholipids that affect various cellular processes through G protein-coupled receptors. In our current study, we found by in situ hybridization that E11.5 mouse embryos strongly expressed the LPA receptor subtype LPA(1) in cartilaginous bone primordia and the surrounding mesenchymal cells. However, despite their wide-ranging actions, the roles of lysophospholipids in chondrogenesis remain poorly understood. The mouse clonal cell line ATDC5 undergoes a sequential differentiation of chondroprogenitor cells in vitro. Undifferentiated and differentiated ATDC5 cells express LPA(1) and other lysophospholipid receptors including S1P receptor S1P(1) and S1P(2). Taking advantage of this cell model, we studied the effects of LPA on the activities of chondroprogenitor cells. LPA markedly stimulates both DNA synthesis and the migration of ATDC5 chondroprogenitor cells in culture, whereas S1P suppresses the migration of these cells. Treatment with Ki16425, an LPA(1)- and LPA(3)-specific receptor antagonist, suppressed the fetal bovine serum-stimulated migration of ATDC5 cells by almost 80%. These results indicate that LPA plays an important role in the activation of chondroprogenitor cells.
溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1P）是生物活性溶血磷脂，通过 G 蛋白偶联受体影响各种细胞过程。在我们目前的研究中，通过原位杂交发现，E11.5 小鼠胚胎在软骨骨原基和周围的间充质细胞中强烈表达 LPA 受体亚型 LPA(1)。然而，尽管它们的作用广泛，但溶血磷脂在软骨发生中的作用仍知之甚少。鼠克隆细胞系 ATDC5 在体外经历软骨祖细胞的顺序分化。未分化和分化的 ATDC5 细胞表达 LPA(1)和其他溶血磷脂受体，包括 S1P 受体 S1P(1)和 S1P(2)。利用这种细胞模型，我们研究了 LPA 对软骨祖细胞活性的影响。LPA 明显刺激 ATDC5 软骨祖细胞在培养中的 DNA 合成和迁移，而 S1P 抑制这些细胞的迁移。用 Ki16425（LPA(1)和 LPA(3)特异性受体拮抗剂）处理可抑制由胎牛血清刺激的 ATDC5 细胞迁移近 80%。这些结果表明 LPA 在软骨祖细胞的激活中发挥重要作用。
