Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China; Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, PR China; School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, PR China.
Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, PR China.
Neuropeptides. 2020 Oct;83:102077. doi: 10.1016/j.npep.2020.102077. Epub 2020 Aug 7.
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.
胚胎骨骼发育是一个复杂的过程,受神经-骨相互作用的调节。血管活性肠肽(VIP)最初被鉴定为一种神经血管扩张剂,后来进一步证明它具有多种生物学功能,如神经递质和免疫调节剂。然而,作为骨骼神经纤维中存在的关键肽类调节剂,VIP 对神经支配和早期骨骼发育调节的功能尚未完全揭示。本研究以鸡胚为实验模型,探讨 VIP 对胚胎骨骼发育的影响。本研究结果证实了周围神经纤维向肢体骨骼组织的神经支配,通过在不同发育阶段的骨骼组织中检测神经丝(NF)和 III 类 β-微管蛋白(TUJ-1)得以证实。骨组织中 VIP mRNA 和肽表达水平也随着神经支配的进展而增加。通过用神经毒素 6-OHDA 暴露鸡胚构建鸡胚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 表达减少。6-OHDA 处理还抑制了远端肢体骨骼发育以及 VIP 的表达。此外,VIP 与 6-OHDA 暴露共同应用可挽救胚胎发生过程中抑制的成骨活性和延迟的骨骼发育。总之,这些结果表明 VIP 在骨骼发育早期的神经支配过程中发挥重要作用。VIP 可恢复化学交感神经切除术诱导的成骨抑制和骨发育损伤。