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New treatments for Ewing's sarcoma (ES) are urgently needed. Magnolol, an active ingredient in Magnolia officinalis, shows anti-oxidative, anti-microbial, and anti-tumor effects, but its effect on ES is unknown. We examined the effect of magnolol on ES cell proliferation and apoptosis in vitro as well as the mechanism of its anticancer effect. The results demonstrated that magnolol inhibited the proliferation of ES and induced ES cell apoptosis through the mitochondrial and death receptor pathways. Magnolol reduced MEK1/2, ERK1/2, and STAT3 phosphorylation in ES cells, suggesting that the MAPK/ERK and JAK/STAT3 signal transduction pathways are involved in the inhibition of ES cell growth by magnolol. In short, magnolol is a potential anti-ES drug., Competing Interests: None., (AJTR Copyright © 2020.)

Background: senile osteoporosis researchers are now seeking to promote osteoblastogenesis and resultant bone formation to directly counteract age-related bone loss. Targeting microRNA (miRNA) activity in adult osteoblasts may be a successful therapeutic strategy for age-related bone loss. We investigated the mechanism(s) by which miRNAs negatively regulate osteoblastogenesis and bone formation in vitro and in vivo . Methods: we performed a miRNA microarray screen followed by PCR validation in adult bone marrow-derived mesenchymal stem cells during the proliferation-to-mineralization transition to identify downregulated miRNAs, most notably miR-451. Primary human calvarial pre-osteoblasts were isolated and transfected with miR-451's agomir or antagomir for in vitro assays. Bioinformatics analysis and in vitro experiments verified YWHAZ as a miR-451 target gene. We next investigated the effects of YWHAZ knockdown on osteoblastic differentiation. To examine the effects of miR-451's antagomir in vivo , we injected ovariectomized (OVX) or sham-operated mice with miR-451's antagomir over a period of six weeks. We isolated stromal cells from murine bone marrow on week six for further ex vivo experimentation. Results: miR-451's antagomir stimulated pre-osteoblast differentiation into a more differentiated, mineralized phenotype. This phenotype was associated with upregulated RUNX2, ALP, and COL1A1 protein expression. miR-451's antagomir derepresses YWHAZ expression, thereby enhancing RUNX2 protein stability and promoting osteoblastic differentiation. When injected in vivo , miR-451's antagomir promotes osteoblastogenesis and mineralization, reversed OVX-induced bone loss, and increased bone strength in OVX and sham-operated mice. Conclusions: miR-451 suppresses osteoblastogenesis in vitro and in vivo . miR-451 inhibition may serve as an effective anabolic therapeutic strategy in senile osteoporosis patients.