Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1949686 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2010 | 8 Pages |
Abstract
Migration of mesenchymal stem cells plays a key role in regeneration of injured tissues. Rheumatoid arthritis (RA) is a chronic inflammatory disease and synovial fluid (SF) reportedly contains a variety of chemotactic factors. This study was undertaken to investigate the role of SF in migration of human bone marrow-derived mesenchymal stem cells (hBMSCs) and the molecular mechanism of SF-induced cell migration. SF from RA patients greatly stimulated migration of hBMSCs and the SF-induced migration was completely abrogated by pretreatment of the cells with the lysophosphatidic acid (LPA) receptor antagonist Ki16425 and by small interfering RNA- or lentiviral small hairpin RNA-mediated silencing of endogenous LPA1/Edg2. Moreover, SF from RA patients contains higher concentrations of LPA and an LPA-producing enzyme autotoxin than normal SF. In addition, SF from RA patients increased the intracellular concentration of calcium through a Ki16425-sensitive mechanism and pretreatment of the cells with the calmodulin inhibitor W7 or calmodulin-dependent protein kinase II inhibitor KN93 abrogated the SF-induced cell migration. These results suggest that LPA-LPA1 plays a key role in the migration of hBMSCs induced by SF from RA patients through LPA1-dependent activation of calmodulin-dependent protein kinase II.
Keywords
PDGF-BBCAMK IIhBMSCsAutotaxinLPAATXα-MEMS1PPTXRT-PCRshRNAMSCsSmall interfering RNAsmall hairpin RNAsiRNA[Ca2+]iα-minimum essential mediumArthritisRheumatoid arthritisOsteoarthritisSphingosine-1-phosphatelysophosphatidic acidMesenchymal stem cellMesenchymal stem cellsHuman bone marrow-derived mesenchymal stem cellspertussis toxinplatelet-derived growth factor-BBsynovial fluidMigrationcalmodulin-dependent protein kinase IIreverse transcription–polymerase chain reaction
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Authors
Hae Young Song, Mi Jeong Lee, Min Young Kim, Kyung Hye Kim, Il Hwan Lee, Sang Hun Shin, Jung Sub Lee, Jae Ho Kim,