Negative Pressure-Regulated microRNA Expression in Apoptotic Vesicles Derived from Bone Marrow Mesenchymal Stem Cells
10.16156/j.1004-7220.2025.04.013
- VernacularTitle:负压调控骨髓间充质干细胞apoVs差异microRNA表达谱
- Author:
Hui WANG
1
;
Yue ZHU
1
;
Shuaishuai ZHANG
1
;
Junrong LI
1
;
Min ZHANG
1
Author Information
1. 口颌系统重建与再生全国重点实验室;国家口腔疾病临床医学研究中心;陕西省口腔医学重点实验室;空军军医大学口腔医院急诊与综合临床科,西安 710032
- Publication Type:Journal Article
- Keywords:
negative pressure;
bone marrow mesenchymal stem cells;
apoptotic vesicles;
microRNA;
osteoarthritis
- From:
Journal of Medical Biomechanics
2025;40(4):886-894
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate changes in the microRNA expression profiles of apoptotic vesicles(apoVs)derived from bone marrow mesenchymal stem cells(BMSCs)under a simulated negative pressure environment,and to provide a theoretical basis for understanding the mechanism by which mechanical stress microenvironments influence the progression of osteoarthritis.Methods A negative pressure cellular environment was established using a pressure-loading system.Cell viability and apoptosis were assessed via the CCK-8 assay,Western blotting,and Annexin V-FITC/PI double staining.ApoVs were isolated by differential centrifugation and characterized using transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blotting.Small RNA sequencing was performed using the HiSeq Single-End mode,and differential expression analysis of microRNAs was conducted using DESeq to screen for differentially expressed microRNAs.The differentially screened microRNAs were validated by real-time quantitative PCR.After treating BMSCs with inhibitors of these differentially expressed microRNAs,the effects of the screened microRNAs on BMSCs were detected.Results Compared to apoVs generated by BMSCs under STS chemical treatment,those produced under a-40 kPa pressure environment showed significantly upregulated miR-183-5p and downregulated miR-3473.GO and KEGG enrichment analyses revealed that these differentially expressed microRNAs affected cell activity and inflammatory responses through multiple signaling pathways.Inhibition of miR-183-5p and miR-3473 expression reduced the proliferative activity of BMSCs.After inhibiting miR-183-5p expression,the levels of inflammatory factors increased.Inhibition of miR-3473 expression did not alter the IL-6 expression level,but significantly increased the TNFα expression level.Conclusions MicroRNAs specifically expressed in BMSC-derived apoVs under negative pressure stimulation may act as critical mechanical signaling mediators,regulating inflammatory response processes to participate in the pathogenesis and progression of arthritis.
