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定量蛋白质组学揭示了补骨圣髓汤促进成骨细胞增殖的药效网络。

Quantitative Proteomics Revealed the Pharmacodynamic Network of Bugu Shengsui Decoction Promoting Osteoblast Proliferation.

机构信息

Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

School of Pharmacy, Lanzhou University, Lanzhou, China.

出版信息

Front Endocrinol (Lausanne). 2022 Jan 25;12:833474. doi: 10.3389/fendo.2021.833474. eCollection 2021.

Abstract

BACKGROUND AND OBJECTIVE

With high morbidity and disability, osteoporosis is a worldwide bone metabolism disease, regulated by complex pathological processes. Insufficient osteogenesis is greatly essential to osteoporosis. Traditional Chinese Medicine, a complex natural herbal medicine system, has increasingly attracted attention all over the world. Bugu Shengsui Decoction, a compound formula for osteoporosis, has significant clinical effects in the treatment of osteoporosis. Yet the detailed mechanisms are unclear. Thus, we investigated the effects and mechanism of Bugu Shengsui Decoction on osteoporotic rats and osteoblasts .

METHODS

In this study, we evaluated the effect of Bugu Shengsui Decoction in an animal model of orchiectomy. Multi-pharmacology indexes revealed that Bugu Shengsui Decoction obviously improved bone metabolism, bone mineral density, bone morphology, and biomechanics in the castrated rats. Then, serum pharmacology was employed to unveil that Bugu Shengsui Decoction promoted the proliferation and differentiation of osteoblasts. Moreover, quantitative proteomics combined with RNA interference assay was used to analyze and verify the pathway and key targets in pro-proliferation of MC3T3-E1 cells.

RESULTS

Bugu Shengsui Decoction obviously improved the worse parameters of bone metabolism, bone mineral density, bone morphology, and biomechanics in a castrated rat model. , Bugu Shengsui Decoction exerted proliferation- and differentiation-promoting effects of osteoblasts induced by serum starvation. Moreover, quantitative proteomics analysis combined with RNA interfere assay illustrated that Bugu Shengsui Decoction promoted osteogenesis the PI3K-AKT pathway.

CONCLUSION

Summarily, our discoveries certify that Bugu Shengsui Decoction is an effective treatment for osteoporosis PI3K-AKT. This study is not only a beneficial attempt to explore the detailed mechanism of Traditional Chinese formula but also will provide inspiration for the treatment strategy of osteoporosis.

摘要

背景与目的

骨质疏松症是一种全球范围内的骨骼代谢疾病,具有较高的发病率和致残率,由复杂的病理过程调节。成骨不足是骨质疏松症的重要原因。中药作为一种复杂的天然草药体系,在全球范围内越来越受到关注。骨股生髓汤是一种治疗骨质疏松症的复方方剂,在治疗骨质疏松症方面具有显著的临床效果。然而,其详细机制尚不清楚。因此,我们研究了骨股生髓汤对骨质疏松症大鼠和成骨细胞的作用及机制。

方法

在这项研究中,我们评估了骨股生髓汤在去势大鼠动物模型中的作用。多药理学指标表明,骨股生髓汤明显改善了去势大鼠的骨代谢、骨密度、骨形态和生物力学。然后,采用血清药理学方法揭示骨股生髓汤促进成骨细胞的增殖和分化。此外,定量蛋白质组学结合 RNA 干扰实验用于分析和验证 MC3T3-E1 细胞增殖前体中的通路和关键靶点。

结果

骨股生髓汤明显改善了去势大鼠模型中骨代谢、骨密度、骨形态和生物力学的恶化参数。骨股生髓汤对血清饥饿诱导的成骨细胞增殖和分化具有促进作用。此外,定量蛋白质组学分析结合 RNA 干扰实验表明,骨股生髓汤通过 PI3K-AKT 通路促进成骨作用。

结论

总之,我们的发现证明了骨股生髓汤是治疗骨质疏松症的有效方法,其作用机制与 PI3K-AKT 有关。本研究不仅是探索中药方剂详细机制的有益尝试,也为骨质疏松症的治疗策略提供了启示。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b9/8822948/e2161b1a3eb7/fendo-12-833474-g001.jpg

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