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小檗碱对小鼠老年性骨质疏松症的保护作用。

Protective effects of berberine on senile osteoporosis in mice.

机构信息

Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Department of Pediatrics, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, People's Republic of China.

出版信息

J Bone Miner Metab. 2021 Sep;39(5):748-756. doi: 10.1007/s00774-021-01225-2. Epub 2021 Apr 8.

Abstract

INTRODUCTION

The incidence of osteoporosis is positively correlated with age. Berberine has been reported to treat osteoporosis due to its beneficial actions on bone formation. However, the direct effects of berberine on senile osteoporosis remain unclear. The present study investigated the protective effects of berberine on senile osteoporosis in mice and preliminarily evaluated its potential mechanism.

MATERIALS AND METHODS

20-month-old male C57BL/6 J mice were used as senile osteoporosis mouse model and treated with strontium ranelate (SR) or berberine or solvent control by daily gavage for 2 months. Thereafter, bone mass and microstructure parameters were assessed. Histological staining was performed to identify the osteogenic, adipogenic and osteoclastic activity of bone tissue. Moreover, role of cAMP/PKA/CREB signaling pathway in berberine affecting bone marrow mesenchymal stem cells (BMSCs) differentiation was clarified by enzyme-linked immunosorbent assay and western blot analysis.

RESULTS

The results showed that the SR-treated group displayed a high trabecular bone mass phenotype. For mice administrated with berberine, cancellous bone mass was upregulated in a dose-dependent manner, as indicated by gradually increased bone mass, trabecular bone volume fraction and trabecular number. Furthermore, berberine promotes osteogenic and inhibits adipogenic differentiation of BMSCs via cAMP/PKA/CREB signaling. Also, bone resorption effect becomes more obvious with increasing dose of berberine in vitro.

CONCLUSION

The present results suggest that berberine exerts potent bone protective effects by promoting bone formation, inhibiting marrow fat accumulation and bone resorption. This effect may be achieved through cAMP/PKA/CREB signaling pathway.

摘要

简介

骨质疏松症的发病率与年龄呈正相关。已有报道称,小檗碱通过促进骨形成来治疗骨质疏松症。然而,小檗碱对老年性骨质疏松症的直接作用尚不清楚。本研究探讨了小檗碱对老年骨质疏松症小鼠的保护作用,并初步评估了其潜在机制。

材料和方法

使用 20 月龄雄性 C57BL/6J 小鼠作为老年性骨质疏松症小鼠模型,通过每日灌胃给予雷奈酸锶(SR)或小檗碱或溶剂对照 2 个月。然后评估骨量和微观结构参数。进行组织学染色以鉴定骨组织的成骨、成脂和成骨细胞活性。此外,通过酶联免疫吸附试验和 Western blot 分析阐明 cAMP/PKA/CREB 信号通路在小檗碱影响骨髓间充质干细胞(BMSCs)分化中的作用。

结果

结果表明,SR 处理组表现出高骨小梁骨量表型。对于给予小檗碱的小鼠,松质骨量呈剂量依赖性上调,表现为骨量、骨小梁体积分数和骨小梁数量逐渐增加。此外,小檗碱通过 cAMP/PKA/CREB 信号促进 BMSCs 的成骨和抑制成脂分化。并且,体外小檗碱剂量增加时,骨吸收作用变得更加明显。

结论

本研究结果表明,小檗碱通过促进骨形成、抑制骨髓脂肪堆积和骨吸收来发挥强大的骨保护作用。这种作用可能是通过 cAMP/PKA/CREB 信号通路实现的。

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