Icariin triggers osteogenic differentiation of bone marrow stem cells by up-regulating miR-335-5p.

BACKGROUND: The physical health and quality of life of the elderly are severely affected by osteoporosis (OP). METHODS: We explored the regulatory mechanism of ICA in vivo and in vitro by constructing OP rats and inducing osteogenic differentiation of BMSCs. First, we determined the expression of miR-335-5p in bone tissues of OP patients, bone tissues of OP rats, and osteogenic BMSCs by RT-qPCR. Alizarin red staining was employed to detect the formation of calcium nodules in the cells. MTT was used to detect cell viability. Finally, we detected the bone tissue changes in OP rats by overexpression of miR-335-5p or oral ICA. RESULTS: miR-335-5p was lowly expressed in bone tissues of OP patients and OP rats. ICA treatment reversed the inhibitory effect of miR-335-5p inhibitor on BMSCs matrix mineralization. Moreover, PTEN was verified to be a downstream effector of miR-335-5p. During ICA induction, overexpression of PTEN reversed the promotive effect of miR-335-5p mimics on the osteogenic differentiation of BMSCs. In vivo experiments also found that overexpression of miR-335-5p or ICA treatment improved the pathogenesis of OP in rats. CONCLUSION: ICA improved OP by up-regulating miR-335-5p to inhibit PTEN, thereby providing a new strategy for the prevention and treatment of OP.

Predictive role of Glutathione S-transferases (GSTs) on the prognosis of osteosarcoma patients treated with chemotherapy.

OBJECTIVE: We conducted a comprehensive study to investigate the role of GSTM1, GSTTI and GSTP1 genetic variation involved in transport pathways in response to chemotherapy and clinical outcome of osteosarcoma. METHODS: A total of 146 patients were included in our study between January 2008 and December 2009. All the patients were followed up to death or January 2012. Genotyping of GSTM1, GSTT1 and GSTP1 was conducted in a 384-well plate format on the Sequenom MassARRAY platform. RESULTS: Sixty seven patients (45.9%) died during the follow-up period. The median age of patients was 14.2 years and ranged from 9.3 to 38.7 years. The median follow-up time was 29.6 months (range 5 to 60 months). Individuals with GSTP1 G/G genotype tended to live shorter than A/A genotype, and we found a significantly higher risk of death from osteosarcoma (adjusted HR=2.73, 95% CI=1.05-7.45). Individuals with the GSTP GG genotype were more likely to have a poor response to chemotherapy, with an OR of 2.73 (95%CI, 1.07-7.81). However, we did not find association of polymorphisms in GSTM1 and GSTT1 with response to chemotherapy and prognosis of osteosarcoma. CONCLUSION: Our study provides information for prediction of treatment outcome in clinical oncology. Due to the limited number of samples, the results of our study need to be confirmed by large sample size studies.