Embryonic bone development is a complicated procedure and modulated by neuro-osteogenic interaction. Vasoactive intestinal peptide (VIP) was first identified as a neural vasodilator and further proved to possess multiple biological functions such as neurotransmitter and immune regulator. However, as a key peptide regulator presented in skeletal nerve fibers, the function of VIP on innervation and early bone development regulation has not fully been uncovered yet. In this study, the chick embryo has been used as an experimental model to address the effect of VIP on embryonic bone development. Our study results confirmed the innervation of peripheral nerve fibers into limb bone tissue, which was revealed by the detection of neurofilament (NF) and class III β-tubulin (TUJ-1) in bone tissue at various developing stages. The VIP mRNA and peptide expression level in bone tissue were also increased upon innervation progress. A chick embryonic chemical sympathectomy model was constructed by exposing chick embryos with neurotoxin 6-OHDA. The 6-OHDA exposure of the early chick embryo caused the reduction of neural crest formation and NF expression. 6-OHDA treatment also inhibited distal limb bone development as well as VIP expression. Furthermore, co-application of VIP with 6-OHDA exposure could rescue the inhibited osteogenesis activity and delayed bone development during embryogenesis. Taken together, these results reveal that VIP played an important role during innervation at early stage of bone development. VIP could restore chemical sympathectomy induced osteogenesis inhibition and bone development impair in chick embryos.

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血管活性肠肽对鸡胚胎骨骼发育的作用研究

胚胎骨发育是一个复杂的过程，受神经-成骨相互作用的调节。血管活性肠肽（VIP）首先被鉴定为神经血管扩张剂，并进一步证明具有神经递质和免疫调节剂等多种生物学功能。然而，作为骨骼神经纤维中存在的关键肽调节剂，VIP在神经支配和早期骨骼发育调节中的功能尚未完全揭示。在这项研究中，鸡胚胎已被用作实验模型来解决 VIP 对胚胎骨骼发育的影响。我们的研究结果证实了周围神经纤维在四肢骨组织中的神经支配，这通过检测不同发育阶段骨组织中的神经丝 (NF) 和 III 类 β-微管蛋白 (TUJ-1) 来揭示。骨组织中 VIP mRNA 和肽的表达水平也随着神经支配的进展而增加。通过将鸡胚胎暴露于神经毒素 6-OHDA 来构建鸡胚胎化学交感神经切除术模型。早期鸡胚的 6-OHDA 暴露导致神经嵴形成和 NF 表达的减少。6-OHDA 治疗还抑制远端肢体骨骼发育以及 VIP 表达。此外，VIP 与 6-OHDA 暴露的共同应用可以挽救胚胎发生过程中受抑制的成骨活性和延迟的骨发育。综上所述，这些结果表明 VIP 在骨骼发育早期的神经支配过程中发挥了重要作用。VIP可以恢复化学交感神经切除术引起的鸡胚胎成骨抑制和骨发育障碍。