Osteogenic Responses of Human Mesenchymal Stromal Cells to Static Stretch

Abstract

Molecular signals driving the regenerative process in distraction osteogenesis (DO) involve a complex system of cellular behavior triggered by mechanical strain. However, it remains unclear how mesenchymal stromal cells (MSCs) adapt to osteogenic demands during DO. We hypothesized that human MSCs (hMSCs) modulate early osteogenic metabolism during exposure to static stretch. The proliferation of hMSCs was increased by static stretch, which, in turn, suppressed TGF-β1-mediated decreases in cell proliferation. The amount of stretching force applied had little effect on osteoblast differentiation of hMSCs induced by dexamethasone treatment. However, this strain induced sustained production of nitric oxide and vascular endothelial growth factor (VEGF), which are critical factors in angiogenesis, from differentiated hMSCs. Mechanical stretch involved ERK and p38 mitogen-activated protein kinase pathways, the selective inhibitors of which decreased static-stretch-induced VEGF production. These findings provide evidence that hMSCs act to facilitate early osteogenic metabolism during exposure to static stretch.