Decreased osteogenesis of adult mesenchymal stem cells by reactive oxygen species under cyclic stretch: a possible mechanism of age related osteoporosis

Abstract

Age related defect of the osteogenic differentiation of mesenchymal stem cells (MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation. Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats. Accordingly, there were much more reactive oxygen species (ROS) production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1 (SOD1) was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.

Dynamic adhesive environment alters the differentiation potential of young and ageing mesenchymal stem cells

“…Our ultimate finding that varying the surrounding adhesive environment has a significant effect on the behavior of stem cells and especially on their differentiation potential is in agreement with some previous reports highlighting the role of mechanical stretching of the underlining substratum [17,46,47]. The role of cyclic stretching on MSCs fate has also received attention [17,[46][47][48], however its significance and mechanism of action are still in debate.…”

“…The role of cyclic stretching on MSCs fate has also received attention [17,[46][47][48], however its significance and mechanism of action are still in debate. One area of advantage of using cyclic stretching is that cell adhesion is tightly linked to the bidirectional cell-ECM mechanotransduction [47] and integrin signaling [34].…”

“…Endothelial cells responded to cyclic shearstress with an increase in stress filaments that led to the regulation of autocrine and paracrine signaling for angiogenesis and vascular remodeling [15,16]. Cyclic stretch was also shown to affect the osteogenic differentiation of MSCs [17] as well as the bone homeostasis [18]. The use of PNIPAM for culturing stem cells has also been previously explored: Shi et al [19] studied the proliferation and multi-differentiation potentials of human mesenchymal stem cells (MSCs) on thermo-responsive PNIPAM grafted PDMS surface showing that the proliferation is not significantly different from that on a surface coated with gelatin.…”

The application of mesenchymal progenitor stem cells for the reduction of oxidative stress in animals

“…Positive results were also obtained in rats suffering from osteoporosis. In older individuals, which received stem cells in the form of injection, an increase in gene expression dismutase 1 (SOD1) was noted, which affects the reduction of reactive oxygen species (Tan et al, 2015). Studies by Sun et al (2015) show that the MSCs isolated from bone marrow contributed to restoring the integrity of the intestinal epithelial barrier in the rat that had been damaged by prolonged exposure to oxidative stress.…”

Powering tyrosol antioxidant capacity and osteogenic activity by biocatalytic polymerization

“…Antioxidant compounds have recently been exploited in tissue engineering as promoters of osteoblast differentiation, 19 since they can counteract the inhibitory effects of reactive oxygen species (ROS) on the process of bone formation by osteoblastic cells. [20][21][22][23] Natural polyphenolic compounds, such as resveratrol and green tea catechins, have been shown to increase alkaline phosphatase (ALP) activity and collagen mineralization by enhancing calcium deposition in mesenchymal stem cells. 24,25 Olive oil polyphenols such as oleuropein and hydroxytyrosol can stimulate the deposition of calcium in osteoblastic MC3T3-E1 cells.…”