RETINOIC ACID DOWN-REGULATES BONE MORPHOGENETIC PROTEIN 7 EXPRESSION IN RAT WITH CLEFT PALATE

摘要

Objective To evaluate the effects of retinoic acid(RA)on expression of bone morphogenetic protein 7(BMP-7)in rat fetus with cleft palate,and the effects of RA on proliferation and apoptosis of osteoblasts.Methods All-trans RA(ATRA)was used to induce congenital cleft palate in Wistar rat.BMP-7 mRNA expression in maxillary bone tissue of fetal rats was measured by Northern blotting analysis.Flow cytometry and MTT assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells.BMP-7 mRNA and protein expressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis.Results ATRA could induce cleft palate of rat fetus.The incidence rate of cleft palate induced by 100 mg/kg ATRA(45.5%)was significantly higher than 50 mg/kg ATRA(12.5%,P<0.05).BMP-7 mRNA expression decreased in maxillary bone tissue of rat fetus with cleft palate.MC-3T3-E1 cells proliferation treated with 1×10-6 mol/LATRA decreased by 60%,the cell apoptosis increased by 2 times.BMP-7 mRNA and protein levels in MC-3T3-E1 cells treated with 1×10-6 mol/L ATRA decreased by 60% and 80%,respectively,compared with ATRA-untreated cells(P<0.05).Conclusions BMP-7 may play an important role in embryonic palate development.RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.