中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (26): 4242-4249.doi: 10.12307/2024.338

• 组织构建综述 tissue construction review • 上一篇    下一篇

山奈酚活性单体治疗骨质疏松症的相关信号通路

杨启培1,陈  锋2,崔  伟2,张  驰2,武瑞骐1,宋振恒1,孟  鑫1   

  1. 1广西中医药大学,广西壮族自治区南宁市  530000;2广西中医药大学附属瑞康医院,广西壮族自治区南宁市  530011
  • 收稿日期:2023-04-26 接受日期:2023-06-03 出版日期:2024-09-18 发布日期:2023-10-07
  • 通讯作者: 崔伟,教授,主任医师,硕士生导师,广西中医药大学附属瑞康医院,广西壮族自治区南宁市 530011
  • 作者简介:杨启培,男,1996年生,新疆维吾尔自治区巴音郭楞蒙古自治州人,汉族,广西中医药大学在读硕士,主要从事脊柱、骨关节创伤性疾病的防治研究。
  • 基金资助:
    广西中医药多学科交叉创新团队项目(GZKJ2310),项目负责人:陈锋;广西自然科学基金项目(2021GXNSFAA220089),项目负责人:陈锋;广西研究生教育创新计划资助项目(YCBZ2021075),项目负责人:张驰

Signaling pathways related to kaempferol active monomers in the treatment of osteoporosis

Yang Qipei1, Chen Feng2, Cui Wei2, Zhang Chi2, Wu Ruiqi1, Song Zhenheng1, Meng Xin1   

  1. 1Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 2Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • Received:2023-04-26 Accepted:2023-06-03 Online:2024-09-18 Published:2023-10-07
  • Contact: Cui Wei, Professor, Chief physician, Master’s supervisor, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • About author:Yang Qipei, Master candidate, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    Guangxi Chinese Medicine Interdisciplinary Innovation Team Project, No. GZKJ2310 (to CF); Guangxi Natural Science Foundation Project, No. 2021GXNSFAA220089 (to CF); Guangxi Postgraduate Education Innovation Program, No. YCBZ2021075 (to ZC)

摘要:


文题释义:

骨质疏松症(osteoporosis,OP):是以骨密度与骨量的下降、骨皮质变薄、骨微结构破坏为特征,导致骨质脆性提升,易发生骨折的一种全身退变性骨病。
山奈酚活性单体:山奈酚是从多种植物中提取出来具有抗炎、抗肿瘤、抗氧化应激、抗过敏的一种黄酮类活性单体,以往的研究多集中在其对肿瘤、肝病、心血管等疾病的作用机制。随着基础研究的深入,发现山奈酚可以通过靶向调控多种信号通路,进而介导骨髓间充质干细胞、成骨细胞、破骨细胞的分化、增殖和凋亡,最终达到防治骨质疏松症的目的。


背景:近年研究表明,骨质疏松症的发生和预防常集中在细胞分子学水平,相关信号通路的作用机制是深入了解骨质疏松症的重要途径。目前,中医药已被证实在抗骨质疏松方面具有显著作用,山奈酚作为新兴的中草药提取物,其抗骨质疏松的有效性及作用机制逐渐得到学者们认可,其临床与基础研究逐渐被大家重视。 

目的:分析、整理国内外文献,进一步了解山奈酚活性单体通过调控相关信号通路发挥抗骨质疏松作用的机制。
方法:以“山奈酚,骨质疏松症,成骨细胞,破骨细胞,骨髓间充质干细胞,信号通路”等为中文检索词,检索中国知网、万方、维普数据库;以“kaempferol,Osteoporosis、Osteoblasts,Osteoclasts,Bone mesenchymal stem cells,Signal pathway”等为英文检索词,检索PubMed、Web of Science、Embase数据库,选择各数据库建库至2023 年2 月的相关文献。

结果与结论:①山奈酚通过参与调控骨髓间充质干细胞、成骨细胞和破骨细胞的分化、增殖和凋亡从而在不同程度上影响骨质疏松症的发生和进展。山奈酚通过对多种信号通路的调控来防治骨质疏松症。②山奈酚通过干预Wnt/β-catenin信号通路调控β-catenin数量以及β-catenin-TCF/LEF复合体形成过程来促进成骨细胞增殖分化,抑制破骨细胞形成。③山奈酚通过干预RANKL/RANK通路维持成骨/破骨细胞动态平衡和骨稳态。④山奈酚通过干预PI3K/Akt信号通路上调相关成骨因子Runx2、Osterix水平及促骨细胞钙化促进成骨。⑤山奈酚通过调控ER/ERK通路干预雌激素缺失导致的破骨分化并抑制活性氧的活性。⑥山奈酚通过干预MAPK通路抑制ERK、JNK、p38/MAPK的表达及降低活性氧生成而保护成骨。⑦山奈酚通过BMP/samd 通路增强成骨因子骨形态发生蛋白2、p-Smad1/5/8、β-catenin和Runx2的表达并抑制过氧化物酶体增殖激活受体表达而促进成骨细胞分化、增殖。

https://orcid.org/0009-0004-5206-6375(杨启培);https://orcid.org/0000-0003-2011-7508(崔伟)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 山奈酚, 骨质疏松症, 成骨细胞, 破骨细胞, 骨髓间充质干细胞, 信号通

Abstract: BACKGROUND: Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level, and the mechanism of related signaling pathways is an important way to further understand osteoporosis. At present, traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis. Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action.
OBJECTIVE: To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature.
METHODS: “Kaempferol, osteoporosis, osteoblasts, osteoclasts, bone marrow mesenchymal stem cells, signaling pathways” were used as Chinese and English search terms to search CNKI, WanFang, VIP, PubMed, Web of Science and Embase databases for relevant literature published from database inception to February 2023.
RESULTS AND CONCLUSION: Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation, proliferation and apoptosis of bone marrow mesenchymal stem cells, osteoblasts and osteoclasts. Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways. Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex. Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis. Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification. Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway. Kaempferol inhibits the expression of ERK, JNK, p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway, thus protecting osteogenesis. Kaempferol enhances the expression of osteogenic factors, bone morphogenetic protein-2, p-Smad1/5/8, β-catenin and Runx2, inhibits the expression of Peroxisome proliferation-activated receptor, and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.

Key words: kaempferol, osteoporosis, osteoblast, osteoclast, bone marrow mesenchymal stem cell, signaling pathway

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