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Abstract：
Impaired bone formation is the main characteristics of glucocorticoid (GC)-induced osteoporosis (GIO), which can be ameliorated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. However, the underlying mechanism is still not entirely clear. In the present study, we determined the parameters related to microstructure and function of bone tissue, bone microcirculation, and TXNIP signaling to investigate the beneficial effects of tanshinol on skeleton and its molecular mechanism in GIO rats. Male Sprague-Dawley rats aged 4 months were administrated orally with distilled water (Con), tanshinol (Tan, 25 mg kg-1 d-1), prednisone (GC, 5 mg kg-1 d-1) and GC plus tanshinol (GC + Tan) for 14 weeks. The results demonstrated that tanshinol played a significant preventive role in bone loss, impaired microstructure, dysfunction of bone metabolism and poor bone quality, based on analysis of correlative parameters acquired from the measurement by using Micro-CT, histomorphometry, ELISA and biomechanical assay. Tanshinol also showed a significant protective effect in bone microcirculation according to the evidence of microvascular perfusion imaging of cancellous bone in GIO rats, as well as the migration ability of human endothelial cells (EA.hy926, EA cells). Moreover, tanshinol also attenuated GC-elicited the activation of TXNIP signaling pathway, and simultaneously reversed the down-regulation of Wnt and VEGF pathway as manifested by using Western-blot method in GIO rats, EA cells, and human osteoblast-like MG63 cells (MG cells). Collectively, our data highlighted that tanshinol ameliorated poor bone health mediated by activation of TXNIP signaling via inhibiting microcirculation disturbance and the following impaired bone formation in GIO rats.
摘要：
骨形成受损是糖皮质激素(GC)诱导的骨质疏松(GIO)的主要特征,这可以通过Tanshinol来改善，从丹参中分离出的水性多酚。然而,潜在的机制仍然不完全清楚。在本研究中,我们确定了与骨组织的微观结构和功能有关的参数，骨微循环，和TXNIP信号传导，探讨丹参素对GIO大鼠骨骼的有益作用及其分子机制。4月龄雄性Sprague-Dawley大鼠口服蒸馏水（Con），Tanshinol(Tan,25mgkg-1d-1)，泼尼松（GC，5mgkg-1d-1）和GC加丹参素（GCTan），共14周。结果表明，丹参素在骨丢失中起着重要的预防作用，受损的微观结构，骨代谢功能障碍和骨质量差，在分析Micro-CT测量得到的相关参数的基础上，组织形态计量学,ELISA和生物力学测定。根据GIO大鼠松质骨微血管灌注成像的证据，丹参素还显示出对骨骼微循环的显着保护作用，以及人类内皮细胞的迁移能力（EA。hy926，EA细胞）。此外，丹参素还减弱了GC引起的TXNIP信号通路的激活，同时逆转GIO大鼠Wnt和VEGF通路的下调,EA细胞,和人成骨细胞样MG63细胞(MG细胞)。总的来说，我们的数据强调,丹参素通过抑制GIO大鼠的微循环障碍和随后的骨形成受损,改善了TXNIP信号激活介导的不良骨健康.
