ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Atherosclerosis and Vascular Medicine
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1572045
This article is part of the Research TopicCardiovascular calcification: disease mechanisms, clinical phenotypes and therapeutic strategiesView all 9 articles
Bone Marrow Mesenchymal Stem Cell-Derived Exosomal microRNA-335 Alleviates Vascular Calcification by Targeting SP1
Provisionally accepted
- 1Tianjin Hospital, Tianjin, China
- 2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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Vascular calcification (VC) is a critical pathological characteristic of cardiovascular diseases like atherosclerosis, frequently linked to phenotypic alterations in vascular smooth muscle cells (VSMCs) and the activation of bone-forming genes. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been shown to significantly attenuate VSMC calcification. To investigate whether BMSC-derived exosomes mitigate VSMC calcification through microRNAs (miRNAs) regulation, we developed an in vitro model using β-glycerophosphate-induced calcification and an in vivo model using vitamin D3-induced calcification. Exosomes were extracted from BMSC culture media via ultracentrifugation and analyzed using transmission electron microscopy and particle size distribution assays. Functional and phenotypic assessments revealed that BMSCderived exosomes markedly reduced VSMC calcification. RT-qPCR analysis further indicated that BMSC-derived exosomes regulate VSMC calcification by modulating rno-miR-335 (miR-335). The miR-335 mimic notably suppressed the expression of the osteogenic regulator RUNX2 in VSMCs.Dual-luciferase reporter assays demonstrated that SP1 is a direct target of miR-335. Exosomal miR-335 inhibited SP1 expression, resulting in reduced mRNA and protein levels of RUNX2. In vivo studies confirmed that agomiR-335 treatment significantly lowered SP1 levels in the aorta of male SD rats, alleviating vitamin D3-induced VC. In conclusion, this study highlights that BMSC-derived exosomes regulate VC via the miR-335/SP1 axis, offering novel molecular targets for treating VC.
Keywords: BMSCs, Exosomes, miR-335, Sp1, RUNX2, Vascular Calcification, VSMCs
Received: 06 Feb 2025; Accepted: 04 Sep 2025.
Copyright: © 2025 Li, Chen, Kong, Liu, Liu, Dai and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mei Huang, Tianjin Hospital, Tianjin, China
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