Department of Orthopedic Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, China.
Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Commun Biol. 2023 Feb 20;6(1):197. doi: 10.1038/s42003-023-04567-x.
The brain-bone regulatory system regulates skeletal homeostasis via bioactive neuropeptides, yet the underlying mechanism remains elusive. Here, we report the role of the neuropeptide VF (NPVF, VPNLPQRF-NH) in enhancing both angiogenesis and osteogenesis in a rat skeletal system and the potential pathways involved. An in vitro study revealed that NPVF not only promotes migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) by activating NPFFR1, which leads to upregulation of miR-181c-3p and downregulation of Argonaute1 (AGO1), but also mediates osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the Wnt/β-catenin signaling pathway. To improve the stability and bioavailability and thus efficacy of NPVF as a promoter of in vivo bone regeneration, we genetically engineered amyloid-NPVF-fusion proteins and utilized them as self-assembling nanofiber coatings to treat bone defects in a rat calvarial defect model. We found that a porous hydroxyapatite scaffold loaded with the NPVF peptide-fused amyloid coating substantially enhanced angiogenesis and site-specific fresh bone in-growth when implanted in calvarial defects. Taken together, our work uncovered a previously undefined crosstalk between the brain and bone by unveiling the role of NPVF in bone tissue and demonstrated a viable method for promoting bone tissue repairs based upon self-assembling NPVF-containing protein coatings.
脑-骨调节系统通过生物活性神经肽调节骨骼动态平衡，但潜在机制仍不清楚。在这里，我们报告了神经肽 VF (NPVF，VPNLPQRF-NH) 在增强大鼠骨骼系统中的血管生成和成骨作用及其潜在途径中的作用。体外研究表明，NPVF 通过激活 NPFFR1 不仅促进人脐静脉内皮细胞 (HUVEC) 的迁移和血管生成，导致 miR-181c-3p 的上调和 Argonaute1 (AGO1) 的下调，而且还通过 Wnt/β-catenin 信号通路介导骨髓间充质干细胞 (BMSCs) 的成骨分化。为了提高 NPVF 作为体内骨再生促进剂的稳定性和生物利用度及功效，我们对淀粉样 NPVF-融合蛋白进行基因工程改造，并将其用作自组装纳米纤维涂层，以治疗大鼠颅骨缺损模型中的骨缺损。我们发现，负载 NPVF 肽融合淀粉样蛋白涂层的多孔羟基磷灰石支架在植入颅骨缺损时，可显著促进血管生成和特定部位的新鲜骨内生长。总之，我们的工作揭示了 NPVF 在骨组织中的作用，揭示了大脑和骨骼之间以前未定义的相互作用，并展示了一种基于自组装 NPVF 含蛋白涂层促进骨组织修复的可行方法。
