{"title":"山奈酚通过抑制 CAV-1 促进骨髓间充质干细胞的成骨分化。","authors":"Yingxue Li, Ying Wang, Qian Liu, Shuiying Lv, Yali Wang, Huanhuan Zhang, Qiuhong Zhao, Lei Shang","doi":"10.1186/s13018-024-05174-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Our study focused on the effects and molecular mechanisms of kaempferol, a major active component of Eucommia ulmoides Oliver (EUO), on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).</p><p><strong>Methods: </strong>Target molecules for EUO, osteoarthritis, and osteogenic differentiation were identified through network pharmacology analysis. BMSCs were isolated and treated with various concentrations of kaempferol. Optimal concentration was determined through MTT assays. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) and Alizarin Red S staining, while osteogenic markers (Collagen I, RUNX2, and OPN) and CAV-1 expression were analyzed using RT-qPCR and Western blot. The effects of combined treatment with kaempferol and an overexpression vector for CAV-1 (oe-CAV-1) on osteogenic differentiation were also observed.</p><p><strong>Results: </strong>Network pharmacology analysis identified kaempferol as the primary active component influencing CAV-1 targeted in subsequent experiments. It was found that 10 µM kaempferol was optimal for treating BMSCs. Post-treatment, significant increases in ALP activity and calcium deposition were observed, along with elevated expression of osteogenic markers, and decreased CAV-1. Overexpression of CAV-1 significantly reversed the promotive effects of kaempferol on BMSC osteogenic differentiation, effectively inhibiting the process.</p><p><strong>Conclusion: </strong>Collectively, kaempferol promotes osteogenic differentiation in BMSCs by inhibiting CAV-1 expression.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"19 1","pages":"678"},"PeriodicalIF":2.8000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495062/pdf/","citationCount":"0","resultStr":"{\"title\":\"Kaempferol promotes osteogenic differentiation in bone marrow mesenchymal stem cells by inhibiting CAV-1.\",\"authors\":\"Yingxue Li, Ying Wang, Qian Liu, Shuiying Lv, Yali Wang, Huanhuan Zhang, Qiuhong Zhao, Lei Shang\",\"doi\":\"10.1186/s13018-024-05174-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Our study focused on the effects and molecular mechanisms of kaempferol, a major active component of Eucommia ulmoides Oliver (EUO), on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).</p><p><strong>Methods: </strong>Target molecules for EUO, osteoarthritis, and osteogenic differentiation were identified through network pharmacology analysis. BMSCs were isolated and treated with various concentrations of kaempferol. Optimal concentration was determined through MTT assays. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) and Alizarin Red S staining, while osteogenic markers (Collagen I, RUNX2, and OPN) and CAV-1 expression were analyzed using RT-qPCR and Western blot. The effects of combined treatment with kaempferol and an overexpression vector for CAV-1 (oe-CAV-1) on osteogenic differentiation were also observed.</p><p><strong>Results: </strong>Network pharmacology analysis identified kaempferol as the primary active component influencing CAV-1 targeted in subsequent experiments. It was found that 10 µM kaempferol was optimal for treating BMSCs. Post-treatment, significant increases in ALP activity and calcium deposition were observed, along with elevated expression of osteogenic markers, and decreased CAV-1. Overexpression of CAV-1 significantly reversed the promotive effects of kaempferol on BMSC osteogenic differentiation, effectively inhibiting the process.</p><p><strong>Conclusion: </strong>Collectively, kaempferol promotes osteogenic differentiation in BMSCs by inhibiting CAV-1 expression.</p>\",\"PeriodicalId\":16629,\"journal\":{\"name\":\"Journal of Orthopaedic Surgery and Research\",\"volume\":\"19 1\",\"pages\":\"678\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-10-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495062/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Orthopaedic Surgery and Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13018-024-05174-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ORTHOPEDICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Orthopaedic Surgery and Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13018-024-05174-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
引用次数: 0
摘要
研究目的我们的研究重点是杜仲（Eucommia ulmoides Oliver，EUO）的主要活性成分山奈酚对骨髓间充质干细胞（BMSCs）成骨分化的影响和分子机制：方法：通过网络药理学分析确定了杜仲、骨关节炎和成骨分化的靶分子。分离 BMSCs 并用不同浓度的山奈酚处理。通过 MTT 试验确定最佳浓度。碱性磷酸酶（ALP）和茜素红 S 染色法评估了成骨分化，RT-qPCR 和 Western 印迹法分析了成骨标志物（胶原 I、RUNX2 和 OPN）和 CAV-1 的表达。此外，还观察了山奈酚和CAV-1过表达载体（oe-CAV-1）联合处理对成骨分化的影响：结果：网络药理学分析确定山奈酚是影响 CAV-1 的主要活性成分，是后续实验的目标。研究发现，10 µM 的山奈酚是处理 BMSCs 的最佳浓度。处理后，观察到 ALP 活性和钙沉积明显增加，成骨标志物表达升高，CAV-1 减少。CAV-1的过度表达明显逆转了山奈酚对BMSC成骨分化的促进作用，有效抑制了这一过程：总而言之，山奈酚通过抑制 CAV-1 的表达促进了 BMSCs 的成骨分化。
Kaempferol promotes osteogenic differentiation in bone marrow mesenchymal stem cells by inhibiting CAV-1.
Objective: Our study focused on the effects and molecular mechanisms of kaempferol, a major active component of Eucommia ulmoides Oliver (EUO), on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).
Methods: Target molecules for EUO, osteoarthritis, and osteogenic differentiation were identified through network pharmacology analysis. BMSCs were isolated and treated with various concentrations of kaempferol. Optimal concentration was determined through MTT assays. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) and Alizarin Red S staining, while osteogenic markers (Collagen I, RUNX2, and OPN) and CAV-1 expression were analyzed using RT-qPCR and Western blot. The effects of combined treatment with kaempferol and an overexpression vector for CAV-1 (oe-CAV-1) on osteogenic differentiation were also observed.
Results: Network pharmacology analysis identified kaempferol as the primary active component influencing CAV-1 targeted in subsequent experiments. It was found that 10 µM kaempferol was optimal for treating BMSCs. Post-treatment, significant increases in ALP activity and calcium deposition were observed, along with elevated expression of osteogenic markers, and decreased CAV-1. Overexpression of CAV-1 significantly reversed the promotive effects of kaempferol on BMSC osteogenic differentiation, effectively inhibiting the process.
Conclusion: Collectively, kaempferol promotes osteogenic differentiation in BMSCs by inhibiting CAV-1 expression.
期刊介绍：
Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues.
Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications.
JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.
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