Ox-LDL Promotes Migration and Adhesion of Bone Marrow-Derived Mesenchymal Stem Cells via Regulation of MCP-1 Expression

Abstract

Bone marrow-derived mesenchymal stem cells (bmMSCs) are the most important cell source for stem cell transplant therapy. The migration capacity of MSCs is one of the determinants of the efficiency of MSC-based transplant therapy. Our recent study has shown that low concentrations of oxidized low-density lipoprotein (ox-LDL) can stimulate proliferation of bmMSCs. In this study, we investigated the effects of ox-LDL on bmMSC migration and adhesion, as well as the related mechanisms. Our results show that transmigration rates of bmMSCs and cell-cell adhesion between bmMSCs and monocytes are significantly increased by treatments with ox-LDL in a dose- and time-dependent manner. Expressions of ICAM-1, PECAM-1, and VCAM-1 as well as the levels of intracellular Ca2+ are also markedly increased by ox-LDL in a dose-dependent manner. Cytoskeleton analysis shows that ox-LDL treatment benefits to spreading of bmMSCs and organization of F-actin fibers after being plated for 6 hours. More interestingly, treatments with ox-LDL also markedly increase expressions of LOX-1, MCP-1, and TGF-β; however, LOX-1 antibody and MCP-1 shRNA markedly inhibit ox-LDL-induced migration and adhesion of bmMSCs, which suggests that ox-LDL-induced bmMSC migration and adhesion are dependent on LOX-1 activation and MCP-1 expression.

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

“…Previous studies showed that the number of circulating EPCs was inversely correlated with total cholesterol, LDL-cholesterol and ox-LDL levels [11,[58][59][60]. However, Zhang et al reported that the transmigration rates of BM mesenchymal stem cells (MSCs) and cell-cell adhesion between BM MSCs and MCs were significantly increased with ox-LDL treatment in a dose-and time-dependent manner [61]. Our previous [36] and present studies demonstrated that ox-LDL could significantly decrease both circulating MNCs and EPCs levels.…”

Oxidized low‐density lipoprotein (ox‐LDL) promotes cardiac differentiation of bone marrow mesenchymal stem cells via activating ERK1/2 signaling

“…We also observed that ox‐LDL could activate ERK1/2 following short‐term (12‐hour) exposure . ERK1/2 are members of the mitogen‐activated protein kinase superfamily that are involved in cell proliferation, differentiation, migration, and apoptosis . Many studies have shown that the transformation of stem cells to cardiomyocytes involved the activation of ERK1/2 in vitro and in vivo .…”

“…In a recent study, we found that ox‐LDL could stimulate proliferation of BM‐MSCs via activation of LOX‐1 receptor . We also observed that ox‐LDL could activate ERK1/2 following short‐term (12‐hour) exposure .…”

Effects of histone deacetylase inhibitors on regenerative cell responses in human dental pulp cells

“…The growth factors FGF2 and VEGF have also been shown to promote the proliferation, migration and adhesion of human periodontal ligament stem cells in vitro (Zhang et al 2013b). Ox-LDL has also been shown to increase the migration and adhesive behaviour of BMSCs via upregulation of MCP-1 expression (Zhang et al 2013a). Studies have also demonstrated that the mRNA expression of CXCR4, FGF2, MCP-1 and SDF-1 is upregulated in response to HDACis (TSA 20 nmol L À1 or VPA 1 mmol L À1 ) in hDPSCs, and subsequently, the Western blot results also confirmed that TSA (20 nmol L À1 ) or VPA (1 mmol L À1 ) increased the expression of chemokines.…”

“…The medium was changed every three days. hDPSCs were characterized by flow cytometry and analysis of multiple lineage differentiation potential as described previously (He et al 2013, Zhang et al 2013a. Cells between passages 2 and 5 were used in all experimentation.…”