Tanshinol alleviates impaired bone formation by inhibiting adipogenesis via KLF15/PPARγ2 signaling in GIO rats

• 来源期刊: 中国药理学报（英文版）
• 关键词: glucocorticoid-induced osteoporosis (GIO) tanshinol resveratrol bone formation Kruppel-like factor 15 (KLF 15) PPARγ 2 adipogenesis
• 年，卷（期）: 2018,（4）
• 页码范围: 633-641
• 页数: 9页
• 语种: 英文
• DOI: 10.1038/aps.2017.134

摘要

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 Western 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.