Abstract: ObjectiveTo investigate the roles of sonic hedgehog(Shh),smoothened(Smo),and bone morphogenetic protein-2(BMP-2) in fluoride-induced primary chondrocyte damage in rats in vitro.MethodsThe primary chondrocytes were obtained from one-week old healthy Sprague-Dawley rats with mechanical-enzyme digestion method and identified with immunohistochemical cells,and then divided into a control group and 5,10,20,and 40 mg/L sodium fluoride(NaF) exposure groups.After the treatment of 48 hours,the viability of the cells was determined with methyl thiazolyl tetrazolium test(MTT);the expressions of protein and mRNA of Smo,Shh,and BMP-2 were detected with Western blot and reverse transcription-polymerase chain reaction(RT-PCR),and the apoptosis was detected with flow cytometry.ResultsCompared with the control group,the vitality for the cells exposed to NaF of 5 and 10 mg/L significantly increased(113.33±11.74% and 127.25±10.24%,P<0.05)but decreased obviously for the cells to NaF of 40 mg/L(73.91±9.94%,P<0.05); the protein and mRNA expressions of Shh,Smo,and BMP-2 were increased along with the increment of fluorine concentration; the apoptosis rate of the cells with 40 mg/L NaF exposure was 11.13±1.20%,significantly higher than that of the control group(P<0.05).ConclusionFluoride can activate hedgehog(Hh) signaling pathway and both Hh signaling pathway and apoptosis may play roles in the pathogenesis of cartilage damage in fluorosis.