RESUMO
Myeloma bone disease (MBD) is one of the most common complications of multiple myeloma (MM). MBD is considered to be caused by the activation of osteoclasts and suppression of osteoblasts resulting from the involvement of neoplastic plasma cells and the change of bone marrow microenvironment. It may be a feasible way to improve the treatment of MBD by promoting osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC), from which the osteoblasts mainly originate. Resveratrol (RES), a naturally occurring polyphenolic flavonoid compound, was reported to function in the modulation of bone metabolism. But the effects of RES on osteogenic differentiation of MM derived BMSC (MM-BMSC) and its underlying mechanism remains unknown. Totally 10 cases of MM-BMSCs were isolated, cultured and identified successfully in the present study. RES was found to promote osteogenic differentiation of MM-BMSC by alkaline phosphatase activity assay, qRT-PCR and alizarin red staining. SIRT1 was predicted to be the target gene of RES in promoting osteogenic differentiation with bioinformatic analysis. RES upregulated the expression of silent information regulator 1 (SIRT1) in MM-BMSC (P<0. 001) and its osteogenic differentiation was inhibited in the SIRT1 small interfering RNA (si-SIRT1) transfected group. Furthermore, the mRNA (P<0. 001) and protein (P<0. 01) expression of runt related transcription factor 2 (RUNX2) was increased in the RES treated group and decreased (mRNA P < 0. 01, protein P < 0. 05) in si-SIRT1 transfected group, respectively. In conclusion, resveratrol promotes osteogenic differentiation of MM-BMSCs via upregulating SIRT1/RUNX2 and seems to be a potential therapeutic agent to counteract bone disease in MM patients.
RESUMO
Objective To compare genomic expression differences between androgenic complete hydatidiform mole (AnCHM) and normal first trimester villi with similar gestation weeks,and search for potential adjuvant diagnostic molecular markers.Methods Short tandem repeat (STR) detection was used to identify AnCHM,human oligonucleotide array U133 Plus 2.0 was used to measure genomic expression differences between AnCHM and normal villi,and quantitative fluorescent RT-PCR was used to verify array of several genes.Results Nine of 11 histologically diagnosed complete hydatidiform moles were found to be AnCHM by means of STR,and the other 2 were biparental complete hydatidifonn mole (BiCHM). Compared with villi,oligonueleotide array showed 279 genes (0.72%,279/38 500) were over expressed and 1710 genes (4.44%,1710/38 500) under expressed in AnCHM.Bioinformatics analysis found that differentially expressed genes were involved in multiple biological processes and pathways.Changes of imprinting genes,growth hormone genes and chorionie somatomammotropin hormone genes were especially remarkable.Conclusions Pathogenesis of AnCHM is a complex process involving multiple genes and pathways.Altered expression of imprint genes may play important roles in the process.
