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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丹参酚通过 KLF15/PPARγ2 信号传导抑制 GIO 大鼠的脂肪生成，从而减轻骨形成受损。


糖皮质激素 (GC) 诱导的骨质疏松症 (GIO) 的特点是骨形成受损，丹参酚可以缓解这种情况，丹参酚是一种从丹参中分离出来的水性多酚。在这项研究中，我们研究了 GC 诱导的成骨调节的分子机制，以及使用丹参酚干扰 GIO 的可能性。 4月龄雌性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），持续 14 周。处死大鼠后，收集骨组织样本。使用显微 CT、组织形态计量学和生物力学测定来评估骨形成的变化。通过蛋白质印迹和定量 RT-PCR 测量骨骼组织中 Kruppel 样因子 15 (KLF15)、过氧化物酶体增殖物激活受体 γ 2 (PPARγ 2) 和其他信号蛋白的表达。 GC处理显着增加了与脂肪生成相关的KLF15、PPARγ2、C/EBPα和aP2的表达，上调了FoxO3a通路蛋白（FoxO3a和Gadd45a），并抑制了经典Wnt信号传导（β-catenin和Axin2），这是必需的用于成骨。因此，GC显着降低骨量和骨质量。与 Tan 或 Res 联合治疗可有效抵消 GC 损伤的骨形成，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，丹参酚通过 KLF15/PPARγ2/FoxO3a/Wnt 通路抑制骨髓肥胖，从而抵消 GC 减少的骨形成。