No abstract

Puerarin, an isoflavone-C-glucoside extracted from the root of Pueraria Labata (Willd.) Ohwi, is one of the most important crude herbs used in Chinese medicine for various medicinal purposes. Accumulating evidence has indicated that puerarin suppresses bone resorption and promotes bone formation. However, the molecular mechanism involved in puerarin-associated bone formation is unclear. The present study aimed to investigate the molecular mechanism of puerarin-induced osteoblast proliferation and differentiation. The study showed that puerarin treatment differentially affected cell proliferation in a time-dependent manner. Notably, at a concentration of 20 µM, puerarin significantly promoted cell proliferation in comparison with the control (P<0.01). Furthermore, puerarin promoted MC3T3-E1 cell differentiation at an appropriate concentration. In addition, miR-106b was significantly upregulated in MC3T3-E1 cells following treatment with 20 µM puerarin (P<0.01), and a known target for miR-106b, receptor activator of nuclear factor-κB ligand (RANKL) was demonstrated using the luciferase reporter assay. Furthermore, inhibition of miR-106b significantly reversed the promotion of cell differentiation induced by puerarin in MC3T3-E1 cells (P<0.01). In conclusion, the present study demonstrated that puerarin exerts its role in MC3T3-E1 osteogenesis through miR-106b by targeting RANKL. The findings suggest that puerarin may be considered a promising anti-osteoporotic agent for the treatment of osteoporosis.

Hypothesis: Polymorphisms of REN, AGTR1 and AGTR2 may be associated with responses of renin-angiotensinaldosterone system (RAAS) activity phenotypes to angiotensin-converting enzyme inhibitor (ACEI) antihypertensive treatment. Materials and methods:A total of 400 first diagnosed Kazak hypertensives were randomly allocated to two groups and received a 3-week course of either captopril and atenolol as monotherapy under double blinding. Genotype-phenotype association analyses were performed by covariance analyses between baseline level and responses of blood pressure, renin, angiotensin II and aldosterone concentrations with tagging single nucleotide polymorphisms (SNPs) in REN, AGTR1 and AGTR2 genes. A false discovery rate method was used to adjust multiple testing. Results: After adjustment for multiple testing, we found that the G allele of rs6676670 (T/G) in intron 1 of REN was significantly associated with higher baseline aldosterone concentrations (p < 0.0001, explained variance (EV) = 2.3%). Significant associations after adjustments were also found between the A allele of rs2887284, with higher baseline renin activity (p = 0.022, EV = 1.0%), higher responses of renin (p = 0.018，EV = 5.4%), and higher responses of angiotensin II (p = 0.0255, EV = 3.13%) to the treatment of ACEI. The carriers of the A allele of rs2887284 appeared to be more sensitive to the ACEI treatment. Conclusion: rs2887284 in intron 9 of REN is associated with the response of renin and angiotensin II levels to ACEI treatment.