RESUMEN
OBJECTIVE:To study the effects of paeonol on Wnt and BMP/Smad pathway in ankylosing spondylitis (AS) model mice,and to investigate prevention and treatment mechanism of paeonol for AS. METHODS:40 mice were randomly divided into normal group,model group,sulfasalazine group(positive control,9 mg/kg)and paeonol group(3 mg/kg),with 10 mice in each group. In addition to the normal group,Freund's adjuvant and proteoglycan were used to establish AS model in each group. After modeling,mice in each administration group were given relevant medicine intragastrically;normal group and model group were given constant volume of distilled water intragastrically,once a day,for consecutive 20 d. After last administration, the mice were killed,TEM was used to observe the ultrastructural pathologic change of synovial cells in articulationes sacroiliaca. The serum contents of TNF-α and DKK-1 were determined by ELISA,and the mRNA expressions of BMP-2,Cbfα1 and Smad1 in synovial tissue were detected by real-time fluorescent quantitative PCR. RESULTS:Compared with normal group,serum content of TNF-α in model group was increased significantly,while serum content of DKK-1 was decreased significantly;mRNA expressions of BMP-2,Cbfα1 and Smad1 in synovial tissue were increased significantly,with statistical significance (P<0.05 or P<0.01). Under the electron microscope,the synoviocytes of mice in model group were proliferated and arranged in disorder,and the secretory activity of active organelles were hyperactivity and the gap among cells became widened. Compared with model group, serum content of TNF-α in sulfasalazine group and paeonol group were decreased significantly;serum content of DKK-1 was increased significantly and mRNA expressions of BMP-2,Cbfα1 and Smad1 in synovial tissue were decreased significantly in paeonol group,with statistical significance (P<0.05 or P<0.01). Electron microscopy showed that mitochondria,lysosome and rough endoplasmic reticulum structure of synovial cell were improved significantly in paeonol group. CONCLUSIONS:The mechanism prevention and treatment of paeonol on AS may be associated with reducing serum content of TNF-α,increasing serum content of DKK-1,down-regulating mRNA expressions of BMP-2,Cbfα1 and Smad1 in synovial cells,inhibiting Wnt and BMP/Smad ossification related signal transduction pathway and reversing osteogenic differentiation of synovial cells.