IGF2BP3通过上调KLK4促进骨髓间充质干细胞成骨分化。

IF 2.8 4区医学 Q3 CELL BIOLOGY

Connective Tissue Research Pub Date : 2025-01-01 Epub Date: 2025-02-23 DOI:10.1080/03008207.2025.2458129

Jiazhu Tang, Guoyang Zhao, Jianzhong Zhao, Bo Wang

{"title":"IGF2BP3通过上调KLK4促进骨髓间充质干细胞成骨分化。","authors":"Jiazhu Tang, Guoyang Zhao, Jianzhong Zhao, Bo Wang","doi":"10.1080/03008207.2025.2458129","DOIUrl":null,"url":null,"abstract":"Background: Osteoporosis (OP) is a chronic metabolic bone disease marked by imbalance in osteoblast and osteoclast activity. This study was aimed to explore the molecular mechanism underlying osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) to discover the novel target for OP.Methods: RT-qPCR was used for mRNA expression detection of Kallikrein 4 (KLK4) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Protein detection was conducted by western blot. The osteogenic differentiation of BMSCs was evaluated through alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Interaction between IGF2BP3 and KLK4 was analyzed using RNA immunoprecipitation (RIP) assay and actinomycin D assay.Results: KLK4 was downregulated in OP patients, and upregulated in osteogenically differentiated BMSCs. KLK4 overexpression promoted the osteogenic differentiation of BMSCs. IGF2BP3 enhanced the expression of KLK4. KLK4 upregulation restored the effect of IGF2BP3 knockdown on the osteogenic differentiation of BMSCs. Moreover, IGF2BP3 overexpression enhanced the osteogenic differentiation of BMSCs by promoting KLK4.Conclusion: These evidences suggested that IGF2BP3 contributed to the osteogenic differentiation of BMSCs via mediating KLK4, providing a potential target for treatment of OP.","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"66 1","pages":"49-58"},"PeriodicalIF":2.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IGF2BP3 facilitates the osteogenic differentiation of bone marrow mesenchyml stem cells via upregulating KLK4.\",\"authors\":\"Jiazhu Tang, Guoyang Zhao, Jianzhong Zhao, Bo Wang\",\"doi\":\"10.1080/03008207.2025.2458129\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Osteoporosis (OP) is a chronic metabolic bone disease marked by imbalance in osteoblast and osteoclast activity. This study was aimed to explore the molecular mechanism underlying osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) to discover the novel target for OP.Methods: RT-qPCR was used for mRNA expression detection of Kallikrein 4 (KLK4) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Protein detection was conducted by western blot. The osteogenic differentiation of BMSCs was evaluated through alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Interaction between IGF2BP3 and KLK4 was analyzed using RNA immunoprecipitation (RIP) assay and actinomycin D assay.Results: KLK4 was downregulated in OP patients, and upregulated in osteogenically differentiated BMSCs. KLK4 overexpression promoted the osteogenic differentiation of BMSCs. IGF2BP3 enhanced the expression of KLK4. KLK4 upregulation restored the effect of IGF2BP3 knockdown on the osteogenic differentiation of BMSCs. Moreover, IGF2BP3 overexpression enhanced the osteogenic differentiation of BMSCs by promoting KLK4.Conclusion: These evidences suggested that IGF2BP3 contributed to the osteogenic differentiation of BMSCs via mediating KLK4, providing a potential target for treatment of OP.\",\"PeriodicalId\":10661,\"journal\":{\"name\":\"Connective Tissue Research\",\"volume\":\"66 1\",\"pages\":\"49-58\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Connective Tissue Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/03008207.2025.2458129\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Connective Tissue Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03008207.2025.2458129","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景：骨质疏松症（Osteoporosis， OP）是一种以成骨细胞和破骨细胞活性失衡为特征的慢性代谢性骨病。本研究旨在探讨骨髓间充质干细胞（BMSCs）成骨分化的分子机制，以发现opp的新靶点。方法：采用RT-qPCR方法检测骨髓间充质干细胞（BMSCs）中钾化因子4 （KLK4）和胰岛素样生长因子2 mRNA结合蛋白3 （IGF2BP3）的mRNA表达。western blot法检测蛋白。碱性磷酸酶（ALP）染色和茜素红（ARS）染色评价骨髓间充质干细胞成骨分化情况。采用RNA免疫沉淀（RIP）法和放线菌素D法分析IGF2BP3与KLK4的相互作用。结果：KLK4在OP患者中表达下调，在成骨分化的BMSCs中表达上调。KLK4过表达促进骨髓间充质干细胞成骨分化。IGF2BP3增强了KLK4的表达。KLK4上调恢复IGF2BP3下调对骨髓间充质干细胞成骨分化的影响。此外，IGF2BP3过表达通过促进KLK4促进骨髓间充质干细胞成骨分化。结论：这些证据表明IGF2BP3通过介导KLK4参与骨髓间充质干细胞成骨分化，为治疗OP提供了潜在的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

IGF2BP3 facilitates the osteogenic differentiation of bone marrow mesenchyml stem cells via upregulating KLK4.

Background: Osteoporosis (OP) is a chronic metabolic bone disease marked by imbalance in osteoblast and osteoclast activity. This study was aimed to explore the molecular mechanism underlying osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) to discover the novel target for OP.

Methods: RT-qPCR was used for mRNA expression detection of Kallikrein 4 (KLK4) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Protein detection was conducted by western blot. The osteogenic differentiation of BMSCs was evaluated through alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Interaction between IGF2BP3 and KLK4 was analyzed using RNA immunoprecipitation (RIP) assay and actinomycin D assay.

Results: KLK4 was downregulated in OP patients, and upregulated in osteogenically differentiated BMSCs. KLK4 overexpression promoted the osteogenic differentiation of BMSCs. IGF2BP3 enhanced the expression of KLK4. KLK4 upregulation restored the effect of IGF2BP3 knockdown on the osteogenic differentiation of BMSCs. Moreover, IGF2BP3 overexpression enhanced the osteogenic differentiation of BMSCs by promoting KLK4.

Conclusion: These evidences suggested that IGF2BP3 contributed to the osteogenic differentiation of BMSCs via mediating KLK4, providing a potential target for treatment of OP.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.