Sphingosine 1-Phosphate Receptor 2 Regulates the Migration, Proliferation, and Differentiation of Mesenchymal Stem Cells.
Mesenchymal stem cells (MSCs) are a multipotent cell population acquired most prominently from bone marrow with the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, and others. MSCs demonstrate the capacity to home to sites of injury and contribute to tissue repair. Sphingosine 1-phosphate (S1P) is a biologically active sphingolipid impacting proliferation, apoptosis, inflammation, and angiogenesis with changes in S1P concentration providing significant implications for various disease conditions including cancer, diabetes, and cardiac disease. These functions are primarily mediated by interactions with 5 G-protein coupled S1P receptors (S1PR1-5). In this paper, we demonstrate that inhibition of S1PR2 results in increased MSC clonogenicity, migration, and proliferation; features dependent on Erk phosphorylation. Furthermore, decreased S1PR2 expression decreases the differentiation of MSCs into adipocytes and mature osteoblasts that may be the result of increased expression of MSC pluripotency factors including Nanog, Sox-9, and Oct-4. Inhibition of S1PR1 and S1PR3 in contrast does not impact MSC migration or Erk activation although increased proliferation is observed. In the study, we describe the essential role of S1PR2 in MSC differentiation pathways through modification of pluripotency factors. We propose a MAPK dependent mechanism through S1PR2 inhibition that promotes equally multipotent MSC proliferation.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
S Tucker
ST
Price
Memorial Sloan Kettering Cancer Center, USA.
Thomas H
TH
Beckham
Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA.
Joseph C
JC
Cheng
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Ping
P
Lu
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Xiang
X
Liu
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
James S
JS
Norris
Erk; Mesenchymal stem cells; Pluripotency factors; S1PR2; Self renewal