title: Lysophosphatidic acid mediates migration of human mesenchymal stem cells stimulated by synovial fluid of patients with rheumatoid arthritis.
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 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.
authors.affiliation: Medical Research Center for Ischemic Tissue Regeneration, the Medical Research Institute, School of Medicine, Pusan National University, Busan, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Song
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Lee
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Kim
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: Lee
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Shin
authors.forename: Jung Sub
authors.initials: JS
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C032881:lysophosphatidic acid