Abstract：
Several neuropeptides present in bone tissues, produced by nerve fibers and bone cells, have been reported to play a role in regulating the fine-tuning of osteoblast and osteoclast functions to maintain bone homeostasis. This study aims to characterize the influence of the neuropeptide vasoactive intestinal peptide (VIP) on the differentiation process of human mesenchymal stem cells (MSCs) into osteoblasts and on their anabolic function. We describe the mRNA and protein expression profile of VIP and its receptors in MSCs as they differentiate into osteoblasts, suggesting the presence of an autocrine signaling pathway in these cells. Our findings reveal that VIP enhances the expression of early osteoblast markers in MSCs under osteogenic differentiation and favors both bone matrix formation and proper cytoskeletal reorganization. Finally, our data suggest that VIP could be exerting a direct modulatory role on the osteoblast to osteoclast signaling by downregulating the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio. These results highlight the potential of VIP as an osteoinductive differentiation factor, emerging as a key molecule in the maintenance of human bone homeostasis.
摘要：
骨组织中存在的几种神经肽，由神经纤维和骨细胞产生，据报道，在调节成骨细胞和破骨细胞功能的微调以维持骨稳态方面发挥作用。本研究旨在表征神经肽血管活性肠肽（VIP）对人骨髓间充质干细胞（MSCs）向成骨细胞分化过程及其合成代谢功能的影响。我们描述了在MSCs分化成成骨细胞时，VIP及其受体的mRNA和蛋白表达谱。提示在这些细胞中存在自分泌信号通路。我们的发现表明，VIP在成骨分化下增强了MSCs中早期成骨细胞标志物的表达，并有利于骨基质的形成和适当的细胞骨架重组。最后,我们的数据表明,VIP可能通过下调核因子-κB受体活化因子配体/骨保护素比值,对成骨细胞向破骨细胞信号传导发挥直接调节作用.这些结果突出了VIP作为骨诱导分化因子的潜力，正在成为维持人体骨骼稳态的关键分子。
