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Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation of mesenchymal stem cells, the molecular mechanism involved remains to be fully elucidated. In this study, we showed that BMP9 simultaneously promotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2 cells. Knockdown of Smad4 with RNA interference reduced nuclear translocation of Smad1/5/8, and disrupted BMP9-induced osteogenic differentiation. BMP9-induced osteogenic differentiation was blocked by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activated Smads singling, and yet PD98059 stimulated Smads singling in C3H10T1/2 cells. The effects of inhibitor were reproduced with adenovirus expressing siRNA targeted p38 and ERK1/2, respectively. Taken together, our findings revealed that Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation. Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatory roles in mediating BMP9-induced osteogenic differentiation of C3H10T1/2 cells. [BMB reports 2012; 45(4): 247-252]

High surface area ceria-titania materials were used as supports for manganese oxide for both warm-gas mercury capture and low temperature selective catalytic reduction. These materials exhibited excellent mercury capture capability at 175 °C. Increasing manganese loadings improves the mercury capacities. In the presence of SO2, only a small decrease in mercury capacity was observed for the CeO2–TiO2 adsorbents. CeO2–TiO2 adsorbents similarly showed excellent stability in the presence of CO and NO. It was also found that the CeO2–TiO2 support can capture Hg0 and Hg2+ simultaneously from nitrogen at 175 °C; the total mercury capacities were high. Brunauer–Emmentt–Teller surface area measurements suggested that increasing manganese loading reduced the surface area due to pore blockage. X-ray diffraction measurements showed that MnOx is in an amorphous state on CeO2–TiO2 materials. X-ray photoelectron spectroscopy (XPS) results indicate that the adsorbed mercury is present as both Hg0 and Hg2+ on these ceria-based materials. The XPS observations also suggest that the incorporation of titanium into the cubic lattice of ceria leads to the formation of more lattice oxygen atoms, leading to greater formation of Hg2+ on the CeO2–TiO2 support.

Background and objectivePrevious studies have suggested a positive link between serum uric acid (UA) and bone mineral density (BMD). In this study, we re-examined the association between UA and BMD and further explored whether this was mediated by skeletal muscle mass in a general Chinese population.MethodThis community-based cross-sectional study was conducted among 3079 (963 men and 2116 women) Chinese adults aged 40–75 years. Face-to-face interviews and laboratory analyses were performed to determine serum UA and various covariates. Dual-energy X-ray absorptiometry was used to assess the BMD and appendicular skeletal muscle mass. The skeletal muscle mass index (SMI = ASM/Height2, kg/m2) for the total limbs, arms, and legs was then calculated.ResultsThe serum UA was graded and, in general, was significantly and positively associated with the BMD and muscle mass, after adjustment for multiple covariates in the total sample. Compared with participants in lowest quartile of UA, those participants in highest quartile showed a 2.3%(whole body), 4.1%(lumbar spine), 2.4%(total hip), and 2.0% (femoral neck) greater BMDs. The mean SMIs in the highest (vs. lowest) quartile increased by 2.7% (total), 2.5% (arm), 2.7% (leg) respectively. In addition, path analysis suggested that the favorable association between UA and BMD might be mediated by increasing SMI.ConclusionThe elevated serum UA was associated with a higher BMD and a greater muscle mass in a middle-aged and elderly Chinese population and the UA-BMD association was partly mediated by muscle mass.

Because dendritic cells (DCs) play critical roles in the pathogenesis of rheumatoid arthritis, modulation of their functions could serve as a novel therapy. In this study, we demonstrated that FTY720 treatment significantly suppressed the incidence and severity of collagen-induced arthritis (CIA) in DBA/1J mice via the modulation of DC functions. In FTY720-treated CIA mice, a decrease in the number of DCs in local draining lymph nodes (LNs) was observed. In vitro, FTY720 inhibited the trafficking of LPS-stimulated bone marrow–derived DCs (BMDCs). Decreased secretion of CCL19 and downregulation of CCR7 on DCs may explain the mechanisms underlying the impairment of DC migration induced by FTY720. In a DC-induced mouse arthritis model, FTY720 treatment also suppressed the incidence and severity of arthritis, which was correlated with a decrease in the migration of injected BMDCs to draining LNs. Although lower levels of costimulatory molecules (CD40, CD80, and CD86) and I-Aq expressed on LN DCs were observed in FTY720-treated mice, in vitro analysis showed no effect of FTY720 on LPS-stimulated BMDC maturation. Furthermore, LN cells from FTY720-treated CIA mice displayed diminished production of proinflammatory cytokines in response to collagen II and Con A stimulation. In addition, the ratio of Th1/Th2 in the draining LNs of mice with DC-induced arthritis was decreased upon FTY720 treatment. This finding was consistent with the fact that FTY720 suppressed IL-12p70 production in cultured BMDCs. Taken together, these results indicate that inhibition of DC migration by FTY720 may provide a novel approach in treating autoimmune diseases such as rheumatoid arthritis.