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杜仲多糖通过 ERK/BMP-2/SMAD 信号通路刺激骨形成来缓解糖皮质激素诱导的骨质疏松。

Eucommia ulmoides Oliver polysaccharide alleviates glucocorticoid-induced osteoporosis by stimulating bone formation via ERK/BMP-2/SMAD signaling.

机构信息

Department of Orthodontics, Hospital of Stomatology, Jilin University, Changchun, 130021, China.

Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China.

出版信息

Sci Rep. 2024 Nov 28;14(1):29647. doi: 10.1038/s41598-024-80859-4.

DOI:10.1038/s41598-024-80859-4
PMID:39609585
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11604974/
Abstract

Osteoporosis (OP) is a metabolic disease characterized by low bone mineral mass owing to osteoblast dysfunction. Eucommia ulmoides Oliver (EuO) is a Chinese herbal medicine traditionally used to treat OP. Here, a polysaccharide purified from the EuO cortex (EuOCP3) was administered to OP mice constructed with dexamethasone (Dex) to investigate its anti-OP activity. EuOCP3 significantly improved Dex-induced bone microarchitecture destruction, increased osteoblast numbers and surface, and stimulated an increase in the expression of osteoblast differentiation markers in the femurs of OP mice. Furthermore, EuOCP3 was applied to MC3T3-E1 cells to further explore its effects on osteoblast differentiation. EuOCP3 significantly promoted osteoblast differentiation and increased the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) and SMAD1/5/8. The EuOCP3-mediated enhancement of osteoblast differentiation-related proteins and phosphorylated SMAD1/5/8 expression levels was strongly suppressed by an ERK inhibitor (PD98059), which confirmed the critical role of ERK signaling in EuOCP3-induced osteoblast differentiation. In summary, EuOCP3 can stimulate bone formation by improving osteoblast differentiation via ERK/BMP-2/SMAD signaling, indicating the potential use of EuOCP3 as a functional ingredient in food products for anti-OP treatment.

摘要

骨质疏松症 (OP) 是一种代谢性疾病,其特征是由于成骨细胞功能障碍导致骨矿物质含量低。杜仲 (EuO) 是一种传统的中草药,用于治疗 OP。在这里,用从杜仲皮层中提取的多糖 (EuOCP3) 给用地塞米松 (Dex) 构建的 OP 小鼠进行给药,以研究其抗 OP 活性。EuOCP3 显著改善了 Dex 诱导的骨微观结构破坏,增加了成骨细胞数量和表面,并刺激了 OP 小鼠股骨中成骨细胞分化标志物的表达增加。此外,EuOCP3 被应用于 MC3T3-E1 细胞,以进一步探索其对成骨细胞分化的影响。EuOCP3 显著促进了成骨细胞分化,并增加了磷酸化细胞外信号调节激酶 1/2 (ERK1/2) 和 SMAD1/5/8 的水平。ERK 抑制剂 (PD98059) 强烈抑制了 EuOCP3 介导的成骨细胞分化相关蛋白和磷酸化 SMAD1/5/8 表达水平的增强,这证实了 ERK 信号在 EuOCP3 诱导的成骨细胞分化中的关键作用。总之,EuOCP3 通过改善成骨细胞分化来刺激骨形成,通过 ERK/BMP-2/SMAD 信号通路,这表明 EuOCP3 作为抗 OP 治疗食品产品中的功能性成分具有潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/cba90d322629/41598_2024_80859_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/5f74978355ae/41598_2024_80859_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/bfc185e06828/41598_2024_80859_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/f92c711b4f96/41598_2024_80859_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/a30309e1fbbe/41598_2024_80859_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/b846c67d355c/41598_2024_80859_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/cba90d322629/41598_2024_80859_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/5f74978355ae/41598_2024_80859_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/bfc185e06828/41598_2024_80859_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/f92c711b4f96/41598_2024_80859_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/a30309e1fbbe/41598_2024_80859_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/b846c67d355c/41598_2024_80859_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bfc/11604974/cba90d322629/41598_2024_80859_Fig6_HTML.jpg

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