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铁皮石斛多糖调节成骨细胞与脂肪细胞分化相关的谱系定向。

Dendrobium officinale polysaccharides regulate age-related lineage commitment between osteogenic and adipogenic differentiation.

机构信息

Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, China.

出版信息

Cell Prolif. 2019 Jul;52(4):e12624. doi: 10.1111/cpr.12624. Epub 2019 Apr 30.

Abstract

OBJECTIVES

Excessive oxidative stress and diminished antioxidant defences could contribute to age-related tissue damage and various diseases including age-related osteoporosis. Dendrobium officinale polysaccharides (DOPs), a major ingredient from a traditional Chinese medicine, have a great potential of antioxidative activity. In this study, we explore the role of DOP in age-related osteoporosis that remains elusive.

MATERIALS AND METHODS

Oxidative stimulation and DOP were used to treat bone marrow mesenchymal stem cells (BMSCs), whose lineage commitment was measured by adipogenic- and osteoblastic-induced differentiation analysis. The oxidative stress and antioxidant capacity of BMSCs under the treatment of DOP were analysed by the level of MDA, SOD. Related mechanism studies were confirmed by qRT-PCR, Western blotting and siRNA transfection. DOP was orally administrated in aged mice whose phenotype was confirmed by micro-CT, immunofluorescence, immunochemistry and calcein double-labelling analysis.

RESULTS

Dendrobium officinale polysaccharide treatment markedly increased osteogenic differentiation of BMSCs, while inhibiting adipogenic differentiation. In vitro, DOP could rescue H2O2-induced switch of BMSCs differentiation fate. However, this effect was abolished in BMSCs when interfered with Nrf2 siRNA. Furthermore, administration of DOP to aged mice significantly increased the bone mass and reduced the marrow adipose tissue (MAT) accompanied with decreased oxidative stress of BMSCs.

CONCLUSIONS

Our study reveals that DOP can attenuate bone loss and MAT accumulation through NRF2 antioxidant signalling, which may represent as potential therapeutic agent for age-related osteoporosis.

摘要

目的

过多的氧化应激和抗氧化防御能力的降低可能导致与年龄相关的组织损伤和各种疾病,包括与年龄相关的骨质疏松症。铁皮石斛多糖(DOPs)是一种中药的主要成分,具有很强的抗氧化活性。在这项研究中,我们探索了 DOP 在仍未被揭示的与年龄相关的骨质疏松症中的作用。

材料与方法

用氧化刺激和 DOP 处理骨髓间充质干细胞(BMSCs),通过成脂和成骨诱导分化分析来测量其谱系定向。通过 MDA、SOD 水平分析 DOP 处理下 BMSCs 的氧化应激和抗氧化能力。通过 qRT-PCR、Western blot 和 siRNA 转染验证相关机制研究。用 DOP 对老年小鼠进行口服给药,通过 micro-CT、免疫荧光、免疫组化和钙黄绿素双标记分析来确认其表型。

结果

铁皮石斛多糖处理显著增加了 BMSCs 的成骨分化,同时抑制了成脂分化。在体外,DOP 可以挽救 H2O2 诱导的 BMSCs 分化命运的转变。然而,当用 Nrf2 siRNA 干扰 BMSCs 时,这种作用被消除。此外,DOP 给药到老年小鼠显著增加了骨量,减少了骨髓脂肪组织(MAT),同时伴随着 BMSCs 氧化应激的降低。

结论

我们的研究表明,DOP 可以通过 NRF2 抗氧化信号减轻骨丢失和 MAT 积累,这可能代表一种治疗与年龄相关的骨质疏松症的潜在治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c39/6668967/186624bd8365/CPR-52-e12624-g001.jpg

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