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Objective To investigate the effects of chronic fluoride and arsenic co-exposure on bone morphogenetic proteins 2 (BMP-2) and runt-related transcription factor 2 (Runx2) gene expressions of bone tissue in rats. Methods One hundred and sixty 8-week-old clean-grade Wistar rats weighting (200 ± 50) g were randomly divided into 16 groups by weight via the random number table method of 10 rats in each group by 2 × 4 factorial experimental design (half female and half male), and treated with different doses of fluoride, arsenite and fluoride plus arsenite in deionized water (untreated control group with 0.0 mg/kg fluoride and 0.0 mg/kg arsenite; low-, moderate- and high-fluoride groups were supplemented with 5.0, 10.0 and 20.0 mg/kg fluoride and 2.5, 5.0 and 10.0 mg/kg arsenite) for 6 months. Rats were divided into control (F0.0As0.0), low fluorine (F5.0As0.0), moderate fluorine (F10.0As0.0), high fluorine (F20.0As0.0), low arsenic (F0.0As2.5), moderate arsenic (F0.0As5.0), high arsenic (F0.0As10.0), low fluorine and low arsenic (F5.0As2.5), low fluorine and moderate arsenic (F5.0As5.0), low fluorine and high arsenic (F5.0As10.0), moderate fluorine and low arsenic (F10.0As2.5), moderate fluorine and moderate arsenic (F10.0As5.0), moderate fluorine and high arsenic (F10.0As10.0), high fluorine and low arsenic (F20.0As2.5), high fluorine and moderate arsenic (F20.0As5.0), high fluorine and high arsenic (F20.0As10.0) groups. The concentrations of urinary fluoride (UF) and urinary arsenic (UAs) were determined as exposure biomarkers via the fluoride ion selective electrode method and the flame atomic fluorescence method. The mRNA expressions of BMP-2 and Runx2 were measured with quantitive real-time PCR. Results There were no dental fluorosis found in F0.0As0.0, F0.0As2.5, F0.0As5.0 and F0.0As10.0 groups, and there was a dose-response relationship between the occurrence of dental fluorosis and fluoride doses. Under exposure of fluorine and arsenic combined with high dose of fluorine (20.0 mg/kg), with increasing of arsenic exposure doses, the degree of injury of dental fluorosis increased (χ2 = 9.124, P < 0.05). Compared with F0.0As0.0 (0.99 ± 0.08, 0.99 ± 0.07), the mRNA expressions of BMP-2 (1.01 ± 0.07, 1.06 ± 0.06, 1.21 ± 0.05) and Runx2 (1.03 ± 0.04, 1.24 ± 0.03, 1.33 ± 0.10) in F5.0As0.0, F10.0As0.0, F20.0As0.0 groups were increased with increasing of fluoride doses. Fluoride had a significant effect on mRNA expressions of BMP-2 and Runx2 (F=3.067, 2.927, P<0.05). There was a significant interaction between fluoride and arsenic combination and BMP-2 and Runx2 mRNA expression levels (F = 3.817, 4.802, P < 0.05). Conclusion When rat is co-exposed to fluorine and arsenic, fluorine plays a leading role on BMP-2 and Runx2 mRNA expressions, and arsenic is indirectly involved in fluoride-induced bone toxicity; fluorine and arsenic has a antagonistic effect on BMP-2 and Runx2 mRNA expressions.
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Objective To investigated the association between bone morphogenetic proteins-2 (BMP-2)gene mutation and coal-burning skeletal fluorosis of children in Zhijin Guizhou.Methods In 2010,121 cases of children with skeletal fluorosis were diagnosed based on the standard X-ray Diagnosis of Skeletal Fluorosis (WS192-1999) in coal-burning skeletal fluorosis areas in Zhijin Guizhou,and 50 cases of them were selected as skeletal fluorosis group.Thirty healthy children free of skeletal fluorosis,rickets and other bone related diseases excluded by X-ray were selected as a control group in the same area.Using polymcrase chain reaction combined with DNA sequencing technology,all three exons of BMP-2 gene were conducted sequence screening in skeletal fluorosis and the control groups to detect gene mutations.Results ①The T insertion mutation on exon 1 between 401-402 bp:the T insertion mutantion genotype frequencies of skeletal fluorosis group and the control group were 27.7％ (13/47)and 7.1％ (2/28),and the difference was statistically significant (x2 =4.600,P ＜ 0.05),adjusted OR value of 4.62(1.94-10.90).②)The 894 bp T→G mutation on exon 2:the TG genotype frequencies of skeletal fluorosis group and the control group were 14.0％ (7/50) and 16.7％(5/30),and the difference were not statistically significant (x2=0.103,P＞ 0.05).③The 1 046 bp A→G mutation on exon 2:the AA,AG,GG genotype frequencies of skeletal fluorosis group and the control group was 30.0％ (15/50),24.0％ (12/50),46.0％ (23/50) and 50.0％ (15/30),20.0％(6/30),30.0％ (9/30),and the differences were not statistically significant (x2 =3.099,P ＞ 0.05).Conclusion Exon 1at 401-402 bp,T insertion mutation and skeletal fluorosis are closely related.The relationship between A→Gmutation in exon 2 at 1 046 bp and skeletal fluorosis is not significant.
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Objective:To study the correlation between the bone morphogenetic proteins (BMP-2) and matrix metalloproteinase-9(MMP-9) in fetal membrane and premature rupture of membranes. Methods: 18 samples were selected separately from each of the following groups: puerpera with term pregnancy in labor, puerpera with term premature rupture of membranes(PROM), puerpera in preterm labor, puerpera with pre-tenm PROM and puerpera with term pregnancy not in labor (control group). After labor, fetal membranes in the rupture site were taken out. Immunobistochemistry and pathologic image multimedia operation system were adopted to semiquantitative analyze the area integrated optical density (AIOD) of the positive expression of BMP-2 and MMP-9. Results:①The AIOD of BMP-2 and MMP-9 positive expression in fetal membranes was higher in term pregnancy in labor group, term PROM group, preterm labor group and PROM group than that in control group. There was statistic difference ( P < 0. 0071). ②The AIOD of BMP-2 and MMP-9 in term PROM group was higher than that in term pregnancy in labor group(P=0.0065,P=0.0069), which was higher in PROM group than that in preterm labor group (P=0.0069, P = 0.0052) and term PROM group P=0.0037, P =0.0065),③There was obviously positive correlation between BMP-2 and MMP-9 expression in the fetal membranes in five groups. ( r_s =0.76159,P<0.0001). Conclusions: The expression of MMP-9 and BMP-2 is closely relevant to the repture of membranes. There is a correlation between BMP-2 and MMP-9 expression in fetal membranes.
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AIM:To determine the effect of rhBMP2 on the migration of human breast cancer cells MCF-7. METHODS:MCF-7 was induced by rhBMP2 (30 ?g/L) for 24 h. Atomic force microscopy (AFM) was used to observe the changes in cell morphology. Cell migration and invasion abilities were assayed by scratch healing and transwell experiments. RESULTS:The formation of lamellipodia and cell polarity together with increased cell length were observed in the cells treated with rhBMP2,whereas lamellipodia of cells in control group were not obvious and the majority of cells tended to be rounder with shorter cell diameter. Compared to control group,scratch healing and transwell experiments showed that the migration and invasion capacity of rhBMP2-induced MCF-7 cells was markedly enhanced. CONCLUSION:rhBMP2 induces human breast cancer cell MCF-7 to present the phenotype of migration and enhances the invasion capacity.