Zoledronic Acid Regulates Osteoclasts via miR-483-5p in the BRONJ.

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral diseases Pub Date : 2025-01-06 DOI:10.1111/odi.15233

Zhiyong Guo, Jiajin Yang, Chunjie Li, Xiufa Tang, Jiyuan Liu

{"title":"Zoledronic Acid Regulates Osteoclasts via miR-483-5p in the BRONJ.","authors":"Zhiyong Guo, Jiajin Yang, Chunjie Li, Xiufa Tang, Jiyuan Liu","doi":"10.1111/odi.15233","DOIUrl":null,"url":null,"abstract":"Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy, with unclear mechanisms. This study investigates the regulatory impact of zoledronic acid (ZOL) on osteoclasts and microRNA (miRNA) expression.Materials and methods: Raw264.7 cells and bone marrow-derived macrophages (BMMs) were used to assess ZOL's effects on proliferation and apoptosis. miRNA array analysis was performed during osteoclastogenesis with ZOL treatment. The role of miR-483-5p was examined using miR-mimics and miR-inhibitors. A rat BRONJ model was established for in vivo validation.Results: A concentration of 2 μM ZOL, which did not affect cell proliferation or apoptosis, was used in subsequent experiments. ZOL altered the expression of 64 miRNAs (39 upregulated, 25 downregulated). miR-483-5p mimics alleviated ZOL-induced inhibition of osteoclastogenesis, actin ring formation, bone resorption, and differentiation marker expression, whereas inhibitors enhanced these effects. In vivo, Ago-miR-483-5p promoted wound healing in the BRONJ model, while Antago-miR-483-5p impaired it.Conclusions: ZOL modulates osteoclast function in BRONJ through miR-483-5p inhibition. miR-483-5p may serve as a novel therapeutic target for BRONJ treatment, providing new insights into managing this complication.","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.15233","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy, with unclear mechanisms. This study investigates the regulatory impact of zoledronic acid (ZOL) on osteoclasts and microRNA (miRNA) expression.

Materials and methods: Raw264.7 cells and bone marrow-derived macrophages (BMMs) were used to assess ZOL's effects on proliferation and apoptosis. miRNA array analysis was performed during osteoclastogenesis with ZOL treatment. The role of miR-483-5p was examined using miR-mimics and miR-inhibitors. A rat BRONJ model was established for in vivo validation.

Results: A concentration of 2 μM ZOL, which did not affect cell proliferation or apoptosis, was used in subsequent experiments. ZOL altered the expression of 64 miRNAs (39 upregulated, 25 downregulated). miR-483-5p mimics alleviated ZOL-induced inhibition of osteoclastogenesis, actin ring formation, bone resorption, and differentiation marker expression, whereas inhibitors enhanced these effects. In vivo, Ago-miR-483-5p promoted wound healing in the BRONJ model, while Antago-miR-483-5p impaired it.

Conclusions: ZOL modulates osteoclast function in BRONJ through miR-483-5p inhibition. miR-483-5p may serve as a novel therapeutic target for BRONJ treatment, providing new insights into managing this complication.

查看原文本刊更多论文

唑来膦酸通过miR-483-5p调控BRONJ中的破骨细胞。

目的：双膦酸盐相关性颌骨骨坏死（BRONJ）是双膦酸盐治疗的严重并发症，机制尚不清楚。本研究探讨唑来膦酸（ZOL）对破骨细胞和microRNA （miRNA）表达的调控作用。材料和方法：采用Raw264.7细胞和骨髓源性巨噬细胞（BMMs）观察ZOL对细胞增殖和凋亡的影响。在ZOL治疗的破骨细胞形成过程中进行miRNA阵列分析。使用miR-mimics和miR-inhibitors检测miR-483-5p的作用。建立大鼠BRONJ模型进行体内验证。结果：2 μM ZOL在后续实验中对细胞增殖和凋亡无影响。ZOL改变64个mirna的表达（39个上调，25个下调）。miR-483-5p模拟物减轻了zol诱导的破骨细胞发生、肌动蛋白环形成、骨吸收和分化标记物表达的抑制，而抑制剂增强了这些作用。在体内实验中，Ago-miR-483-5p促进BRONJ模型的伤口愈合，而Antago-miR-483-5p则使其受损。结论：ZOL通过抑制miR-483-5p调节BRONJ破骨细胞功能。miR-483-5p可能作为BRONJ治疗的新治疗靶点，为管理这一并发症提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.