Ultra-small nanodots coated with oligopeptides providing highly negative charges to enhance osteogenic differentiation of hBMSCs better than osteogenic induction medium

For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ostogenesis and clearly reveal the influence factor.To this end,the fluorescent gold nanodots(Au NDs) with highly negative charges as osteogenic induction reagent are successfully synthesized,which display better than commercial osteogenic induction medium through the investigations of ALP activity(2.5 folds) and cytoskeleton staining(1.5 folds).Two kinds of oligopeptides with different bio-structures(cysteine,Cys and glutathione,GSH) are selected for providing surficial charges on Au NDs.It is revealed that Au-Cys with more negative charges(-51 mV) play better role than Au-GSH(-19 mV) in osteogenic differentiation,when both of them have same size(~2 nm),sphere shape and show similar cell uptake amount.To explore deeply,osteogenesis related signaling pathways are monitored,revealing that the enhancement of osteogenic differentiation was through autophagy signaling pathway triggered by Au-Cys.And the promotion of highly negative charges in osteogenic diffe rentiation was further proved via sliver nanodots(Ag NDs,Ag-Cys and Ag-GSH) and carbon nanodots(CDs,Cys-CDs and GSH-CDs).This work indicates part of insights during hBMSCs differentiation and provides a novel strategy in osteogenic differentiation process.

Therapeutic effects of isoquercetin on ovariectomy-induced osteoporosis in mice

Bone marrow mesenchymal stem cells(BMSCs)are non-hematopoietic multipotent stem cells capable of differentiating into mature cells.Isoquercetin,an extract from natural sources,has shown promise as a potential treatment for osteoporosis.To investigate the therapeutic effects of isoquercetin on osteoporosis,bone marrow mesenchymal stem cells(BMSCs)were cultured in vitro,and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days.We evaluated cell viability,osteogenic and adipogenic differentiation,as well as mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts,and mRNA expression levels of Pparγ,Fabp4,and Cebpαin adipocytes.The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation,as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts(P<0.05).In contrast,isoquercetin inhibited adipogenic differentiation and decreased the mRNA expres-sion levels of Pparγ,Fabp4,and Cebpαin adipocytes(P<0.05).In vivo,isoquercetin treatment increased bone quan-tity and density in an osteoporosis model mice group,as determined byμCT scanning and immunohistochemistry(P<0.05).These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.