Hiraki Stimulatory actions of lysophosphatidic acid on mouse ATDC5 chondro progenitor cells
Hiraki Stimulatory actions of lysophosphatidic acid on mouse ATDC5 chondro progenitor cells
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Hiraki 溶血磷脂酸对小鼠 ATDC5 软骨祖细胞的刺激作用
DOI：
10.1007/s00774-010-0184-1
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Y
中科院分区：
文献类型：
--
作者：
R. Itoh;S. Miura;S. Kondo;H. Sano;Y
溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1 P）是具有生物活性的溶血磷脂，通过G蛋白偶联受体影响各种细胞过程。本研究通过原位杂交发现，E11.5小鼠胚胎骨软骨原基及其周围的间充质细胞强烈表达LPA受体亚型LPA 1。然而，尽管溶血磷脂具有广泛的作用，但其在软骨形成中的作用仍知之甚少。小鼠克隆细胞系ATDC 5在体外经历软骨祖细胞的顺序分化。未分化和分化的ATDC 5细胞表达LPA 1和其他溶血磷脂受体，包括S1 P受体S1 P1和S1 P2。利用此细胞模型，我们研究了LPA对软骨祖细胞活性的影响。LPA显着刺激DNA合成和迁移的ATDC 5软骨祖细胞培养，而S1 P抑制这些细胞的迁移。用Ki 16425（一种LPA 1和LPA 3特异性受体拮抗剂）处理，可抑制胎牛血清刺激的ATDC 5细胞迁移近80%。这些结果表明LPA在软骨祖细胞的活化中起重要作用。
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 LPA1in 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 LPA1and other lysophospholipid receptors including S1P receptor S1P1and S1P2. 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 LPA1- and LPA3-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.