Institute for Health and Sport (IHES), Victoria University, Melbourne, VIC, Australia; Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St Albans, VIC, Australia.
Institute for Health and Sport (IHES), Victoria University, Melbourne, VIC, Australia.
Mol Metab. 2021 Jul;49:101205. doi: 10.1016/j.molmet.2021.101205. Epub 2021 Mar 6.
The bone-derived protein osteocalcin (OC), in its undercarboxylated (ucOC) form, has a beneficial effect on energy metabolism and may be a future therapeutic target for metabolic diseases. Increasing evidence suggests a link between ucOC and cardiovascular disease (CVD) development; however, the exact relationship is conflicting and unclear.
The aim of this review was to summarise the current research examining the interaction between OC and vascular dysfunction, the initiating stage in the development of atherosclerosis and CVD.
In humans, the association between OC and vascular function is inconsistent. Several studies report that total OC (tOC) is associated with adverse function or beneficial function, whereas others report that tOC and ucOC has no effect on vascular function. The conflicting data are likely due to several methodological inconsistencies, in particular the lack of studies reporting circulating ucOC levels. In animal models, the direct administration of ucOC to isolated blood vessels ex vivo produced minimal changes in endothelial function, but importantly, no adverse responses. Finally, in human endothelial and vascular smooth muscle cells, ucOC treatment did not influence classical markers of cellular function, including endothelin-1, vascular adhesion molecule-1 and monocyte chemoattractant protein-1 after exposure to high glucose and inflammatory conditions. The lack of adverse effects in ex vivo and in vitro studies suggests that ucOC may be targeted as a future therapeutic for metabolic diseases, without the risk of detrimental effects in the vasculature. However, further studies are needed to confirm these findings and to investigate whether there is a direct beneficial influence of ucOC.
骨源性蛋白骨钙素（OC）在其未羧化（ucOC）形式下对能量代谢有有益影响，可能成为代谢性疾病的未来治疗靶点。越来越多的证据表明 ucOC 与心血管疾病（CVD）发展之间存在关联；然而，确切的关系存在冲突和不明确。
本综述的目的是总结目前研究中检查 OC 与血管功能障碍之间的相互作用，血管功能障碍是动脉粥样硬化和 CVD 发展的起始阶段。
在人类中，OC 与血管功能之间的关联并不一致。一些研究报告称总 OC（tOC）与不良功能或有益功能相关，而其他研究报告称 tOC 和 ucOC 对血管功能没有影响。这些相互矛盾的数据可能是由于几个方法学上的不一致，特别是缺乏报告循环 ucOC 水平的研究。在动物模型中，ucOC 的直接给药对离体血管的内皮功能产生最小的变化，但重要的是，没有不良反应。最后，在人类内皮细胞和血管平滑肌细胞中，ucOC 处理在暴露于高葡萄糖和炎症条件下后，并没有影响细胞功能的经典标志物，包括内皮素-1、血管细胞黏附分子-1 和单核细胞趋化蛋白-1。离体和体外研究中缺乏不良反应表明，ucOC 可能作为代谢性疾病的未来治疗靶点，而不会对血管系统产生有害影响。然而，需要进一步的研究来证实这些发现，并研究 ucOC 是否有直接的有益影响。
