ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1631039
Resveratrol ameliorates osteogenic differentiation, calcification and apoptosis of VSMCs through regulating JNK/Bax signaling
Provisionally accepted
- Heze Medical College, Heze, China
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Vascular calcification involves pathological mineralization in vascular wall, which is characterized by the transformation of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a synthetic phenotype. VSMC undergoing apoptosis were found in vascular calcified plaques. However, the regulatory role of resveratrol in vascular calcification via VSMC apoptosis modulation remains unclear.In calcifying medium (CM)-induced rat VSMC calcification, resveratrol treatment effectively attenuated calcification of VSMCs, as evidenced by reduced calcium content, alkaline phosphatase (ALP) activity and osteogenic markers including Runx2, BMP2, and Osterix levels. Furthermore, resveratrol treatment significantly suppressed TUNEL-positive cell proportions and caspase-3 activity in CM-treated VSMCs. Mechanistically, resveratrol treatment blocked JNK/Bax activation by reducing p-JNK and Bax levels in CM-treated VSMCs. The JNK inhibitor SP600125 markedly reduced calcification, downregulated osteogenic markers and inhibited apoptosis in CM-treated VSMCs. JNK activation reversed resveratrol's anti-calcification and anti-apoptotic effects. In vitamin D3-induced calcification models, resveratrol significantly reduced the vascular calcification and osteogenic differentiation. Collectively, resveratrol exerted an inhibitory effect on VSMC calcification, osteogenic differentiation and apoptosis through inhibition of JNK/ Bax signaling pathway.
Keywords: resveratrol, calcification, JNK/Bax signaling, vascular smooth muscle cells, Apoptosis
Received: 11 Jun 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Hou, Wang, Cheng, Duan, Ren and Lu. 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: Menglin Hou, Heze Medical College, Heze, China
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