Abstract

Osteoporosis is a common bone and metabolic disease that is characterized by bone density loss and microstructural degeneration. Human bone marrow-derived mesenchymal stem cells have great potential for bone tissue engineering and cell-based therapy due to their excellent multipotency, especially osteogenic differentiation. Although low fluid shear force plays an important role in bone osteogenic differentiation, the cellular and molecular mechanisms underlying this effect remain poorly understood due to a lack of effective tools to detect gene expression at the single-cell level. Here, we presented a double-stranded nucleic acid biosensor to examine the regulatory role of Notch signaling during osteogenic differentiation. The effects of orbital shear stress on hMSC proliferation, morphology change, osteogenic differentiation and Notch1-Dll4 signaling were examined. Osteogenic differentiation was studied by characterizing alkaline phosphatase (ALP) activity. We further investigated how orbital shear modulates Notch1-Dll4 signaling during osteogenic differentiation. Our results showed Notch1-Dll4 signaling is involved in orbital shear-regulated osteogenic differentiation. Inhibition of Notch signaling will mediate the effects of shear stress on human osteogenic differentiation.

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