Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

Abstract

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 PPARc2, C/EBPa, adipsin, collagen 1a, osteopontin, ALP, collagen 11a, collagen 2a, and aggrecan, were significantly higher in AQP5 -/ --differentiating BMMSCs, supporting an increased differentiation capacity of AQP5BMMSCs. 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.

Fibroblast Growth Factor-10 (FGF-10) Mobilizes Lung-resident Mesenchymal Stem Cells and Protects Against Acute Lung Injury

“…2 ). Immunofluorescence studies of these BAL-derived cells demonstrated expression of the MSC marker CD105, the mesenchymal cell marker vimentin and the water channel aquaporin-5 (AQP5) as previously described for bone marrow-derived MSCs 29 ( Fig. 2 ).…”

Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

“…For instance, sweat shows acidic pH levels, between 4.6 and 5.4 [56], and in the skin the protective sweat acid mantle acidity ranges from 4 to 5.5 [56]; the pH of human stomach is highly acidic, usually from 1 to 2; osteoclasts’ acidic microenvironment below pH 5.5 is critical for the bone resorption [57]; an acidic pH luminal fluid microenvironment is important for sperm maturation [58]. Interestingly, AQP5 was found expressed in sweat glands [59], gastric mucosa [60], bone cells [61], and in the epididymis [58]. In all these tissues, effective mechanisms of water flux regulation induced by pH fluctuations might be advantageous to prevent excessive water reabsorption and control cell volume and shape.…”

Inhibition of AQP1 Hampers Osteosarcoma and Hepatocellular Carcinoma Progression Mediated by Bone Marrow-Derived Mesenchymal Stem Cells

“…In the last decades, many studies focused attention on the possible involvement of aquaporins (AQPs), a family of proteins characterized for their particular ability to regulate water and solute trafficking along membrane, with tumor progression [ 8 ]. Recent findings demonstrated that water homeostasis regulated by aquaporins represents an important mechanism at the basis of numerous processes such as cancer cell differentiation [ 9 , 10 ] and proliferation as well as apoptosis [ 11 ]. Moreover, aquaporins seem to be involved in tumor cell migration [ 12 ] and thus, in tumor spread and metastasis because of their sensitivity to changes in extracellular osmolality [ 13 ].…”