Objective      To investigate the effect of resveratrol (RES) on hypertrophic differentiation of pre-chondrocyte cells (ATDC5) and related mechanism.       Methods      ATDC5 cells were treated with basal culture medium with different concentrations of RES for 24 h and 48 h

followed by CCK-8 assay. The hypertrophy inducing system was established. ATDC5 cells were divided into control group (0 μmol/L) and RES group (1 μmol/L). The expression levels of hypertrophy-related factors including RUNX2

MMP13 and collagens X (COLX) were detected using qRT-PCR and Western blotting. Toluidine blue staining for GAG and immunohistochemistry for COLX and RUNX2 were performed. Expression levels of altered transcriptional factors and key molecules in canonical chondrogenic pathways including WNT

IHH and FGF were examined by qRT-PCR.       Results      RES with concentration below 1 μmol/L had no toxic effect in this experiment. After induction with hypertrophy medium for 14 d

the hypertrophy of ATDC5 cells was increased after RES treatment. The treated ATDC5 cells showed a significant increase both at the mRNA and protein levels of hypertrophy-related genes including RUNX2

MMP13 and COLX on day 3

day 7

and day 14. The expression levels of β-catenin and GLI2 in the RES group were increased and that of  GLI3 was decreased significantly. Expression of PI3K was not changed in the RES group.       Conclusion      RES promotes hypertrophy of ATDC5 cells by up-regulating β-catenin and GLI2

down-regulating GLI3 and promoting expression of RUNX2.