RRC ID 62028
著者 Roelofsen T, Akkers R, Beumer W, Apotheker M, Steeghs I, van de Ven J, Gelderblom C, Garritsen A, Dechering K.
タイトル Sphingosine-1-phosphate acts as a developmental stage specific inhibitor of platelet-derived growth factor-induced chemotaxis of osteoblasts.
ジャーナル J Cell Biochem
Abstract The development and maintenance of a healthy skeleton depends on the migration of cells to areas of new bone formation. Osteoblasts, the bone forming cells of the body, mature from mesenchymal stem cells under the influence of bone morphogenetic protein. It is unclear at what developmental stage the osteoblasts start to migrate to their functional location. We have studied migration of immature pre-osteoblasts and of mature osteoblasts in response to Platelet-derived growth factor (PDGF) and sphingosine-1-phosphate (S1P). PDGF is a growth factor involved in bone remodeling and fracture healing whereas S1P is a circulating sphingolipid known to control cell trafficking. Our data indicate that PDGF acts as a chemotactic cue for pre-osteoblasts. In contrast, S1P is a chemorepellent to these cells. Upon Bone Morphogenetic Protein 2-induced conversion to the osteoblast phenotype, the chemotaxis response to PDGF is retained whereas the sensitivity to S1P is lost. By RNA interference and overexpression experiments we showed that the expression level of the S1P2 receptor is the sole determinant controlling responsiveness to S1P. The combined data indicate that migration of osteoblasts is controlled by the balance between PDGF, S1P and the differentiation state of the cells. We propose that this mechanism preserves the osteoprogenitor pool in the bone marrow, only allowing the more differentiated cell to travel to sites of bone formation.
巻・号 105(4)
ページ 1128-38
公開日 2008-11-1
DOI 10.1002/jcb.21915
PMID 18819098
MeSH Animals Cell Differentiation Cells, Cultured Chemotaxis / drug effects* Humans Lysophospholipids / pharmacology* Mice Osteoblasts / cytology* Osteogenesis Proto-Oncogene Proteins c-sis / antagonists & inhibitors Proto-Oncogene Proteins c-sis / pharmacology* Receptors, Lysosphingolipid / physiology* Sphingosine / analogs & derivatives* Sphingosine / pharmacology
IF 4.237
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最多言及媒体 Patent(IFI CLAIMS)
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過去6か月間でのオルトメトリクス指標の変動値 0.0
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)