Strontium Regulates Stem Cells Fates During Osteogenic Differentiation Through an Asymmetric Cell Division

Strontium as a popular osteogenic component has been incorporated into various types of orthopaedic biomaterials to enhance bone regeneration. It performs dual effects in promoting bone formation and inhibiting bone resorption. Studies have focused on the effects of strontium in regulating stem cells behaviors to initiate regenerative capacity. However, the mechanism of strontium on regulating stem cells fates and homeostasis has not been fully elucidated. In this study, the promoted effect of strontium on osteogenic differentiation of mesenchymal stem cells was confirmed both in vitro and in vivo. Interestingly, in responding to strontium treatment, stem cells performed asymmetric cell division to balance stemness maintenance and osteogenic differentiation. Asymmetric distribution of Par complex in daughter stem cells induced different cell fates by discriminately activating of osteogenic transcription factors. Strontium activated noncanonical Wnt signaling to regulate Par complex distribution. Understanding the mechanism of strontium on regulating stem cell fate could facilitate biomaterials designing to initiate endogenous bone regenerative capacity.