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Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone formation,which can be alleviated by tanshinol,an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge.In this study we investigated the molecular mechanisms underlying GC-induced modulation of osteogenesis as well as the possibility of using tanshinol to interfere with GIO.Female SD rats aged 4months were orally administered distilled water (Con),prednisone (GC,5 mg·kg-1·d1),GC plus tanshinol (Tan,16 mg·kg-1·d-1) or GC plus resveratrol (Res,5 mg·kg-1·d-1) for 14 weeks.After the rats were sacrificed,samples of bone tissues were collected.The changes in bone formation were assessed using Micro-CT,histomorphometry,and biomechanical assays.Expression of Kruppel-like factor 15 (KLF15),peroxisome proliferator-activated receptor γ 2 (PPARγ 2) and other signaling proteins in skeletal tissue was measured with Weste blotting and quantitative RT-PCR.GC treatment markedly increased the expression of KLF15,PPARγ2,C/EBPα and aP2,which were related to adipogenesis,upregulated Fox03a pathway proteins (Fox03a and Gadd45a),and suppressed the canonical Wnt signaling (β-catenin and Axin2),which was required for osteogenesis.Thus,GC significantly decreased bone mass and bone quality.Co-treatment with Tan or Res effectively counteracted GC-impaired bone formation,suppressed GC-induced adipogenesis,and restored abnormal expression of the signaling molecules in GIO rats.We conclude that tanshinol counteracts GC-decreased bone formation by inhibiting marrow adiposity via the KLF15/PPARγ2/Fox03a/Wnt pathway.