Objective To evaluate the efficacy and safety of FTY720 (fligolimod) in different dosages in the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS), so as to provide references for clinical practice. Methods Such databases as MEDLINE, EMbase, The Cochrane Liabrary, CBM and CNKI were searched for collecting randomized controlled trials (RCTs) of FTY720 in the treatment of RRMS, which were published from January 1, 2001 to December 31, 2010. The studies were retrieved and the data were extracted according to the predefined inclusion and exclusion criteria, the quality of included studies was evaluated with improved Jadad scale, and the Meta-analyses were performed with RevMan5.1 software. Results Three high quality RCTs were included. The Meta-analyses showed that: a) compared with the control group, orally taking FTY720 could obviously decreased the annualized relapse rate (OR=-6.67, 95%CI -10.75 to -2.60, P=0.001), the confirmed disability progression rate (OR=0.64, 95%CI 0.47 to 0.87, P=0.004), and the incidence rate of intensified lesion on T2-weighted magnetic resonance imaging scans (OR=0.28, 95%CI 0.21 to 0.37, Plt;0.00001); b) There was no significant difference (P=0.55) between the small dosage (0.5mg/d) group and the big dosage (1.25mg/d) group of FTY720; and c) The incidence of adverse events was significantly different among the 3 dosage groups (5mg/d, 1.25mg/d and 0.5mg/d), and the minimum dosage group (0.5mg/d) was safer than the other groups. Conclusion FTY720 is safe to treat RRMS, and it can obviously decrease the annualized relapse rate, confirmed disability progression rate and incidence rate of intense lesion on T2-weighted magnetic resonance imaging scans. There is no dosage-effect relationship found in treating RRMS with FTY720 in different dosages, but the 0.5mg/d FTY720 as the minimum dosage is the safest.
ObjectiveTo investigate the effect of FTY720-P on the differentiation and maturation of MC3T3-E1 cells.MethodsThe MC3T3-E1 cells were divided into the experimental group and the control group. In the experimental group, the cells were induced by the medium containing 400 ng/mL FTY720-P (chloroform as solubilizer) in vitro. In the control group, the cells were cultured with the medium only containing chloroform. The cell morphology of 2 groups were observed by inverted phase contrast microscope; the expression of osteoblast related protein (collagen type Ⅰ and collagen type Ⅲ) was detected by immunofluorescence staining; the alkaline phosphatase (ALP) staining and alizarin red staining were used to observe the formation of osteoblasts and the formation of mineralized nodules in 2 groups; and the TUNEL fluorescence assay was used to detect the cell apoptosis.ResultsAfter 48 hours of culture, the cells of 2 groups had grown into slender fusiform at the bottom of the bottle, and there was no significant difference in cell morphology between 2 groups. Immunofluorescence staining showed that the expression of collagen type Ⅰ was positive in the experimental group and weakly positive in the control group; the integrated absorbance (IA) value of the experimental group was 187 600±7 944, which was significantly higher than that of the control group (14 230±1 070) (t=43.680, P=0.001). The expression of collagen type Ⅲ was weakly positive in the experimental group and the control group, and there was no significant difference in IA value between 2 groups (t=1.976, P=0.119). ALP staining and alizarin red staining were positive in the experimental group and negative in the control group. TUNEL staining was positive in the experimental group and negative in the control group; the rate of TUNEL staining positive cells in the experimental group was 35.82%±2.99%, which was significantly higher than that in the control group (2.28%±0.51%) (t=23.420, P=0.002).ConclusionFTY720-P can promote the osteogenic differentiation of MC3T3-E1 cells with speeding up maturation and mineralization of extracellular matrix and affect the apoptosis of the cells.
ObjectiveTo investigate the effects of FTY720-P on EphA2-EphrinA2 bidirectional signaling in osteoclasts.MethodsMurine RAW264.7 macrophages were induced into osteoclasts by dexamethasone and 1α, 25-dihydroxyvitamin D3, and identified by tartrate resistant acid phosphatase (TRAP) staining. Then, the osteoclasts were divided into 2 groups. The osteoclasts were treated with 400 ng/mL FTY720-P in experimental group and without FTY720-P in control group, respectively. After 48 hours of culture, the cells in 2 groups were detected by real-time fluorescent quantitative PCR, Western blot, and immunofluorescence staining. The expressions of EphA2, EphrinA2, RhoA, and the bone reconstruction associated proteins［bone morphogenetic protein 2 (BMP-2) and transform growth factor β1 (TGF-β1)］were analyzed and compared.ResultsRAW264.7 cells were successfully induced into osteoclasts identified by TRAP staining. Compared with control group, the relative expressions of EphA2 and EphrinA2 mRNAs and proteins in experimental group significantly decreased after 48 hours (P<0.05), and the relative expression of RhoA protein also significantly decreased (P<0.05). The relative expressions of BMP-2 and TGF-β1 mRNAs were significantly increased (P<0.05), and those protein expressions were enhanced.ConclusionFTY720-P can down-regulate the expression of RhoA and promote the expressions of TGF- β1 and BMP-2 by affecting the transduction of EphA2-EphrinA2 bidirectional signaling in osteoclasts.