Document Detail

Lysophosphatidic acid mediates migration of human mesenchymal stem cells stimulated by synovial fluid of patients with rheumatoid arthritis.
MedLine Citation:
PMID:  19733258     Owner:  NLM     Status:  MEDLINE    
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 LPA(1)/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-LPA(1) plays a key role in the migration of hBMSCs induced by SF from RA patients through LPA(1)-dependent activation of calmodulin-dependent protein kinase II.
Hae Young Song; Mi Jeong Lee; Min Young Kim; Kyung Hye Kim; Il Hwan Lee; Sang Hun Shin; Jung Sub Lee; Jae Ho Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-03
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1801     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-11-30     Completed Date:  2010-06-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  23-30     Citation Subset:  IM    
Medical Research Center for Ischemic Tissue Regeneration, the Medical Research Institute, School of Medicine, Pusan National University, Busan, Republic of Korea.
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MeSH Terms
Arthritis, Rheumatoid / metabolism*
Bone Marrow Cells / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Cell Movement / physiology*
Cells, Cultured
Lysophospholipids / metabolism*
Mesenchymal Stem Cells / cytology*,  metabolism
Receptors, Lysophosphatidic Acid / metabolism
Synovial Fluid / chemistry*,  metabolism
Reg. No./Substance:
0/Lysophospholipids; 0/Receptors, Lysophosphatidic Acid; 22002-87-5/lysophosphatidic acid; EC Protein Kinase Type 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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