PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway.

This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males). Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6), type ΙΙ procollagen gene (COL2A1), cartilage oligomeric matrix protein (COMP), aggrecan (AGC1), type ΙX procollagen gene (COL9A2) and collagen type 1 alpha 1 (COL1A1) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The expressions of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and extracellular regulated protein kinase (ERK) were measured. Overexpressing PDK2 promoted cell viability, adhesion and inhibited cell migration in MSCs (all P<0.05). qRT-PCR assay showed a potent increase in the mRNA expressions of all chondrogenesis markers in response to overexpressing PDK2 (P<0.01 or P<0.05). PDK2 overexpression also induced a significant accumulation in mRNA and protein expressions of JNK, p38MAPK and ERK in MSCs compared to the control (P<0.01 or P<0.05). Meanwhile, silencing PDK2 exerted the opposite effects on MSCs. This study shows a preliminary positive role and potential mechanisms of PDK2 in chondrogenic differentiation of MSCs. It lays the theoretical groundwork for uncovering the functions of PDK2 and provides a promising basis for repairing cartilage lesions in osteoarthritis.

Association of AGTR1 gene A1166C polymorphism with the risk of heart failure: a meta-analysis.

The aim of this study was to investigate the correlation between the A1166C polymorphism in the angiotensin II type 1 receptor (AT1R) gene and heart failure (HF) risk using meta­analysis. The PubMed database was searched, and data were extracted independently by two reviewers. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. Statistical analysis was performed using the STATA 12.0 software. The results of the meta­analysis showed no significant association between the AT1R A1166C polymorphism and HF risk (AA vs CC: OR = 0.72, 95%CI = 0.31-1.68; AA vs AC: OR = 0.78, 95%CI = 0.52-1.18; dominant model: OR = 1.37, 95%CI = 0.92-2.04; recessive model: OR = 0.73, 95%CI = 0.30-1.75). In the subgroup analysis by ethnicity, the results also showed no significant association between A1166C polymorphism and susceptibility to HF in both Caucasian and Asian populations. In conclusion, this meta-analysis suggests that the A1166C polymorphism in AT1R may not be associated with susceptibility to HF. Further large and well-designed studies are needed to confirm these conclusions.

Effect of GBOT on blood lipid and blood glucose metabolism in rats with atherosclerosis.

We observed the variation in in vivo blood lipid and blood glucose metabolism in rats with atherosclerosis after 5-(3,4-dihydroxy-phenyl)-1-piperidin-1-yl-penta-2,4-dien-1-one (GBOT) administration. Wistar rats aged 10 weeks received a high-fat diet to establish the atherosclerosis model. Metabolic indices related to blood lipid and blood glucose were measured before modeling and at 4 and 8 weeks after modeling. Liver fat levels in rats were measured at 8 weeks to analyze the relationship between liver fat and blood lipid levels. We examined the mechanism of blood lipid reduction. The levels of serum triglycerides, total cholesterol, and very-low-density lipoprotein cholesterol in rats in the control group were significantly decreased (P < 0.05) compared with those in the 4-week control group at 4 weeks and decreased significantly and continuously until the 8th week (P < 0.05). Compared with the 8-week control group, the blood glucose level in rats in the 8-week experimental group decreased significantly (P < 0.05), and the level of insulin sensitivity index decreased significantly (P < 0.05). Compared with the control group, triglyceride and total cholesterol levels per unit mass in rat liver tissue in the 8-week experimental group decreased significantly (P < 0.05). Western blotting indicated that GBOT significantly increased the expression of lecithin-cholesterol acyltransferase, low-density lipoprotein receptor, and cholesterol 7 alpha-hydroxylase proteins. GBOT can significantly decrease the levels of blood lipid and blood glucose in rat models of atherosclerosis, and its mechanism may be associated with the promotion of expression of lecithin-cholesterol acyltransferase, low-density lipoprotein receptor, and cholesterol 7 alpha-hydroxylase proteins.