Double-edged effects and mechanisms of Zn²⁺ microenvironments on osteogenic activity of BMSCs: osteogenic differentiation or apoptosis

Abstract

Dual-directional regulation of diverse Zn2+ microenvironments on osteogenic activity of BMSCs plays important roles in the design of zinc-containing biomaterials.

Dual Ion Releasing Nanoparticles for Modulating Osteogenic Cellular Microenvironment of Human Mesenchymal Stem Cells

“…However, moderate amounts of Zn ions can promote osteogenic differentiation of stem cells through upregulation of the ERK pathway, especially increasing the expression of RUNX2 [ 16 , 17 ]. In addition, similar to previous studies, Zn ions promoted osteogenic differentiation of stem cells when the concentration of Zn ions was less than 20 μg/mL [ 28 , 30 ]. Therefore, we have concluded that Zn ions delivered through the ZIOs promoted the early osteogenic gene expression and osteogenic differentiation capacity of hMSCs when treated with 5 μg/mL of ZIOs within 3 days.…”

“…Zinc ions also act as signaling molecules, affecting intracellular signaling pathways [ 27 ]. High concentrations of Zn ions not only decrease bone differentiation capacity, but also induce apoptosis [ 28 , 29 ]. However, moderate amounts of Zn ions can promote osteogenic differentiation of stem cells through upregulation of the ERK pathway, especially increasing the expression of RUNX2 [ 16 , 17 ].…”

Regeneration of Bone Defects in a Rabbit Femoral Osteonecrosis Model Using 3D-Printed Poly (Epsilon-Caprolactone)/Nanoparticulate Willemite Composite Scaffolds

“…The osteoconductive role of Zn 2+ on osteoblasts and mesenchymal stem/stromal cells is highly concentration-dependent [ 34 , 48 ]. The survival and proliferation of mesenchymal stem/stromal cells or MC3T3-E1 accrue in the range of 8 to 12 μM Zn 2+ [ 48 , 49 ].…”

Biological Roles and Delivery Strategies for Ions to Promote Osteogenic Induction

“…As previously described, this pathway is known to stimulate the expression of genes such as BMP2, which is well-known to be involved in osteogenesis and bone formation (Kim et al, 2013 ). Low concentrations of zinc (2 and 5 μg/mL) have also been described to stimulate osteogenesis in rBMSCs through the activation of MAPK-ERK pathway (Yu et al, 2020 ). However, higher zinc concentrations (15 μg/mL) have been shown to induce cell apoptosis by ROS generation (Yu et al, 2020 ).…”

“…Low concentrations of zinc (2 and 5 μg/mL) have also been described to stimulate osteogenesis in rBMSCs through the activation of MAPK-ERK pathway (Yu et al, 2020 ). However, higher zinc concentrations (15 μg/mL) have been shown to induce cell apoptosis by ROS generation (Yu et al, 2020 ).…”