Stimulatory actions of lysophosphatidic acid on mouse ATDC5 chondroprogenitor cells

• Published in: Journal of bone and mineral metabolism 2010-11, Vol.28 (6), p.659-671
• Main Authors: Itoh, Ryota, Miura, Shigenori, Takimoto, Aki, Kondo, Shunya, Sano, Hiroko, Hiraki, Yuji
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone and Bones - cytology; Bone and Bones - embryology; Bone and Bones - metabolism; Cell Line; Cell Migration Inhibition - drug effects; Cell Movement - drug effects; Cell Proliferation; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - metabolism; Chondrogenesis - drug effects; Diseases of the osteoarticular system; DNA - biosynthesis; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; In Situ Hybridization; Isoxazoles - pharmacology; Lysophospholipids - metabolism; MAP Kinase Signaling System; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred ICR; Migration; Original Article; Orthopedics; Propionates - pharmacology; Protein Isoforms - antagonists & inhibitors; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Receptors, Lysophosphatidic Acid - antagonists & inhibitors; Receptors, Lysophosphatidic Acid - genetics; Receptors, Lysophosphatidic Acid - metabolism; Receptors, Lysosphingolipid - genetics; Receptors, Lysosphingolipid - metabolism; RNA, Small Interfering; Sphingosine - analogs & derivatives; Sphingosine - metabolism
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s00774-010-0184-1

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.