期刊
JOURNAL OF BONE AND MINERAL METABOLISM
卷 28, 期 6, 页码 659-671出版社
SPRINGER JAPAN KK
DOI: 10.1007/s00774-010-0184-1
关键词
ATDC5 cells; Lysophosphatidic acid; Sphingosine-1-phosphate; Cell migration; Chondroprogenitor cells
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (SIP) 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, and other lysophospholipid receptors including SIP receptor S1P(1) and SI P-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 SI P 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.
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