Atherosclerotic calcification often coincides with osteoporosis, suggesting a potential interplay between bone and vascular mineralization. Osteoblast-derived matrix vesicles (Ost-MVs), pivotal in bone mineralization, have emerged as potential contributors to ectopic vascular calcification. However, the precise role of Ost-MVs in vascular calcification and the underlying mechanisms remain elusive. In this study, we observed a concomitant increase in atherosclerotic calcification and bone loss, accompanied by elevated release of Ost-MVs into circulation. We demonstrate that circulating Ost-MVs target plaque lesions in the setting of atherosclerosis. Mechanistically, vascular injury facilitates transendothelial transport of Ost-MVs, collagen І remodeling promotes Ost-MVs aggregation, and vascular smooth muscle cell (VSMC) phenotypic switching enhances MV uptake. These pathological changes during atherosclerosis collectively contribute to Ost-MVs recruitment into the vasculature. Furthermore, Ost-MVs and VSMC-derived matrix vesicles (VSMC-MVs) exacerbate calcification via the Ras-Raf-ERK pathway. Our findings unveil a novel Ost-MVs-mediated mechanism participating in vascular calcification and enriching our understanding of bone-vascular crosstalk.

中文翻译：

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成骨细胞的基质囊泡促进动脉粥样硬化钙化


动脉粥样硬化钙化通常与骨质疏松同时发生，这表明骨和血管矿化之间存在潜在的相互作用。成骨细胞衍生的基质囊泡（Ost-MV）在骨矿化中至关重要，已成为异位血管钙化的潜在贡献者。然而，Ost-MV 在血管钙化中的确切作用及其潜在机制仍不清楚。在这项研究中，我们观察到动脉粥样硬化钙化和骨质流失同时增加，并伴随着 Ost-MV 释放到循环中的增加。我们证明循环中的 Ost-MV 在动脉粥样硬化的情况下靶向斑块病变。从机制上讲，血管损伤促进 Ost-MV 的跨内皮转运，胶原蛋白 І 重塑促进 Ost-MV 聚集，血管平滑肌细胞 (VSMC) 表型转换增强 MV 摄取。动脉粥样硬化期间的这些病理变化共同导致 Ost-MV 募集到脉管系统中。此外，Ost-MV 和 VSMC 衍生基质囊泡 (VSMC-MV) 通过 Ras-Raf-ERK 途径加剧钙化。我们的研究结果揭示了一种新的 Ost-MVs 介导的参与血管钙化的机制，丰富了我们对骨血管串扰的理解。