The Expression of HMGB1 in Bone Marrow MSCs Is Upregulated by Hypoxia with Regulatory Effects on the Apoptosis and Adhesion.

Abstract

Background and Aims. Hypoxia regulates the survival of mesenchymal stem cells (MSCs) but the mechanism is unclear. In hypoxia, the level of high mobility group box 1 (HMGB1) was increased in many cells which may be involved in the regulation of cell biology. The aim is to determine whether hypoxia affects the expression of HMGB1 in bone marrow MSCs (BM-MSCs) and to investigate the role of HMGB1 in the apoptosis and adhesion. Methods. BM-MSCs were exposed to hypoxia (1% O2) and normoxia (20% O2) and the expression of HMGB1 was measured by RT-PCR and western blotting. The apoptosis and adhesion of BM-MSCs were evaluated after interfered by different concentrations of HMGB1. Results. Expression of HMGB1 in BM-MSCs showed a significant upregulation in hypoxia when compared to those in normoxia. The adhesion of BM-MSCs was increased by HMGB1 in a concentration-dependent manner; the apoptosis effect of HMGB1 depended on its concentrations: HMGB1 at low concentration (50 ng/mL) promoted the apoptosis of BM-MSCs while HMGB1 at high concentration (≥100 ng/mL) reduced this apoptosis. Conclusions. Hypoxia enhanced the expression of HMGB1 in BM-MSCs with influences on apoptosis and adhesion and this could have a significant effect on the regenerative potential of MSC-based strategies.