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 4 months were orally administered distilled water (Con), prednisone (GC, 5 mg·kg-1·d-1), 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 FoxO3a pathway proteins (FoxO3a 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/FoxO3a/Wnt pathway.

中文翻译：

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丹参醇通过抑制GIO大鼠中经由KLF15 /PPARγ2信号传导的脂肪形成而减轻受损的骨形成。

糖皮质激素（GC）诱导的骨质疏松症（GIO）的特征是骨骼形成受损，丹参酚是一种丹参酚，可以减轻丹参酚的含量，丹参酚是一种从丹参丹参中提取的水性多酚。在这项研究中，我们研究了GC诱导的成骨调节的分子机制，以及使用丹参醇干扰GIO的可能性。给4个月大的雌性SD大鼠口服蒸馏水（Con），泼尼松（GC，5 mg·kg-1·d-1），GC加丹参酚（Tan，16 mg·kg-1·d-1）或GC加白藜芦醇（Res，5 mg·kg-1·d-1）治疗14周。处死大鼠后，收集骨组织样品。使用Micro-CT，组织形态测定法和生物力学测定法评估骨形成的变化。Kruppel样因子15（KLF15）的表达，用Western印迹和定量RT-PCR测量骨骼肌组织中的过氧化物酶体增殖物激活受体γ2（PPARγ2）和其他信号蛋白。GC处理显着增加了与脂肪形成相关的KLF15，PPARγ2，C /EBPα和aP2的表达，上调了FoxO3a途径蛋白（FoxO3a和Gadd45a），并抑制了所需的经典Wnt信号（β-catenin和Axin2）。用于成骨。因此，GC显着降低了骨量和骨质量。与Tan或Res共同治疗可有效抵消GC受损的骨形成，抑制GC诱导的脂肪生成，并恢复GIO大鼠中信号分子的异常表达。我们得出的结论是，丹参酚可通过KLF15 /PPARγ2/ FoxO3a / Wnt途径抑制骨髓肥胖来抵消GC减少的骨形成。