RESUMEN
Shikonin, as a traditional Chinese herbal medicine with a role of anti-cancer, anti-inflammatory, anti-bacterial and other effects. However, there are few studies on the effect of shikonin on osteoporosis. Therefore, the purpose of this study aims to investigate the role and mechanism of shikonin on differentiation of BMSCs and BMMs into osteoblasts and osteoclasts formation. In our study, we treated the cells with different concentrations of shikonin, and then illuminated its effect on oteogenesis and osteoclast differentiation by ALP/alizarin red staining, ALP activity, qRT-PCR, immunofluorescence, Western blot, and TRAP staining. The result showed that shikonin may promote BMSCs differentiate into osteoblasts through the Wnt/ß-catenin signaling pathway. At the same time, it may also inhibit the formation of osteoclasts mediated by RANK/RANKL/OPG pathway in vitro. Our research explains excellently the mechanism of shikonin alleviating osteoporosis in vitro, which maybe contributing to the exploration of a new way to prevent osteoporosis.
RESUMEN
Functional pancreatic neuroendocrine tumours (PNETs) are mainly represented by insulinoma, which secrete insulin independent of glucose and cause hypoglycaemia. The major genetic alterations in sporadic insulinomas are still unknown. Here we identify recurrent somatic T372R mutations in YY1 by whole exome sequencing of 10 sporadic insulinomas. Further screening in 103 additional insulinomas reveals this hotspot mutation in 30% (34/113) of all tumours. T372R mutation alters the expression of YY1 target genes in insulinomas. Clinically, the T372R mutation is associated with the later onset of tumours. Genotyping of YY1, a target of mTOR inhibitors, may contribute to medical treatment of insulinomas. Our findings highlight the importance of YY1 in pancreatic ß-cells and may provide therapeutic targets for PNETs.