水通道蛋白-5缺乏时骨髓源性间充质干细胞的分化能力增强

Ma, T.; Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, China; email:math108@gmail.com

Mesenchymal stem cells (MSCs) are adult stem cells with a self-renewal and multipotent capability and express extensively in multitudinous tissues. We found that water channel aquaporin-5 (AQP5) is expressed in bone marrow-derived MSCs (BMMSCs) in the plasma membrane pattern. BMMSCs from AQP5 -/- mice showed significantly lower plasma membrane water permeability than those from AQP5 +/+ mice. In characterizing the cultured BMMSCs from AQP5 -/- and AQP5 +/+ mice, we found no obvious differences in morphology and proliferation between the 2 genotypes. However, the multiple differentiation capacity was significantly higher in AQP5 -/- than AQP5 +/+ BMMSCs as revealed by representative staining by Oil Red O (adipogenesis); Alizarin Red S and alkaline phosphatase (ALP; osteogenesis); and type II collagen and Safranin O (chondrogenesis) after directional induction. Relative mRNA expression levels of 3 lineage differentiation markers, including PPARγ2, C/EBPα, adipsin, collagen 1a, osteopontin, ALP, collagen 11a, collagen 2a, and aggrecan, were significantly higher in AQP5 -/- -differentiating BMMSCs, supporting an increased differentiation capacity of AQP5 -/- BMMSCs. Furthermore, a bone-healing process was accelerated in AQP5 -/- mice in a drill-hole injury model. Mechanistic studies indicated a significantly lower apoptosis rate in AQP5 -/- than AQP5 +/+ BMMSCs. Apoptosis inhibitor Z-VAD-FMK increased the differentiation capacity to a greater extent in AQP5 +/+ than AQP5 -/- BMMSCs. We conclude that AQP5-mediated high plasma membrane water permeability enhances the apoptosis rate of differentiating BMMSCs, thus decreasing their differentiation capacity. These data implicate AQP5 as a novel determinant of differentiation of BMMSCs and therefore a new molecular target for regulating differentiation of BMMSCs during tissue repair and regeneration. Copyright © 2012, Mary Ann Liebert, Inc. 2012.

Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, China