Bone repair is intricately correlated with vascular regeneration, especially of type H vessels. Sirtuin 1 (SIRT1) expression is closely associated with endothelial function and vascular regeneration; however, the role of SIRT1 in enhancing the coupling of type H vessel formation with osteogenesis to promote bone repair needs to be investigated. A co-culture system combining human umbilical vein endothelial cells and osteoblasts was constructed, and a SIRT1 agonist was used to evaluate the effects of SIRT1 activity. The angiogenic and osteogenic capacities of the co-culture system were examined using short interfering RNA. Mouse models with bone defects in the femur or mandible were established to explore changes in type H vessel formation and bone repair following modulated SIRT1 activity. SIRT1 activation augmented the angiogenic and osteogenic capacities of the co-culture system by activating the PI3K/AKT/FOXO1 signalling pathway and did not significantly regulate osteoblast differentiation. Inhibition of the PI3K/AKT/FOXO1 pathway attenuated SIRT1-mediated effects. The SIRT1 activity in bone defects was positively correlated with the formation of type H vessels and bone repair in vivo, whereas SIRT1 inhibition substantially weakened vascular and bone formation. Thus, SIRT1 is crucial to the coupling of type H vessels with osteogenesis during bone repair.

中文翻译：

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SIRT1 激活通过增强 H 型血管形成和成骨的耦合来促进骨修复

骨修复与血管再生密切相关，尤其是 H 型血管。Sirtuin 1（SIRT1）表达与内皮功能和血管再生密切相关；然而，SIRT1在增强H型血管形成与成骨耦合以促进骨修复方面的作用还需要研究。构建人脐静脉内皮细胞与成骨细胞共培养体系，并使用SIRT1激动剂评价SIRT1活性的影响。使用短干扰RNA检查共培养系统的血管生成和成骨能力。建立股骨或下颌骨骨缺损的小鼠模型，以探索调节 SIRT1 活性后 H 型血管形成和骨修复的变化。SIRT1 激活通过激活 PI3K/AKT/FOXO1 信号通路增强共培养系统的血管生成和成骨能力，并且不会显着调节成骨细胞分化。PI3K/AKT/FOXO1 通路的抑制减弱了 SIRT1 介导的作用。骨缺损中的SIRT1活性与体内H型血管的形成和骨修复呈正相关，而SIRT1抑制则显着削弱血管和骨形成。因此，SIRT1 对于骨修复过程中 H 型血管与成骨的耦合至关重要。