Vasoactive Intestinal Peptide Promotes Fracture Healing in Sympathectomized Mice.
6-OHDA
Fracture healing
Sympathetic nervous systems
Vasoactive intestinal peptide
Journal
Calcified tissue international
ISSN: 1432-0827
Titre abrégé: Calcif Tissue Int
Pays: United States
ID NLM: 7905481
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
17
10
2020
accepted:
30
01
2021
pubmed:
18
5
2021
medline:
16
10
2021
entrez:
17
5
2021
Statut:
ppublish
Résumé
Vasoactive intestinal peptide (VIP) as a neuromodulator and neurotransmitter played a significant role in modulating bone homeostasis. Our previous study reported an essential role of VIP in in vitro BMSCs osteogenesis and in vivo bone defect repair. VIP was also revealed to have a promoting effect on embryonic skeletal element development. However, the role of VIP in fracture healing is not known yet. We hypothesized that the disorder of sympathetic nervous system impairs bone structure and fracture healing, whereas VIP may rescue the sympathetic inhibition effects and promote fracture healing. We employed a 6-hydroxydopamine (6-OHDA) induced sympathectomy mice model (sympathectomized mice), in which successful sympathetic inhibition was confirmed by a decreased level of norephedrine (NE) in the spleen. In the sympathectomized mice, the femoral micro-architecture, bone density and mechanical properties were all impaired compared to the vehicle control mice. The femoral fracture was created in the vehicle or sympathectomized mice. Vehicle mice were locally injected with PBS as a negative control, and the sympathectomized mice were treated with injection of PBS or VIP. VIP expression at the fracture site was significantly decreased in sympathectomized mice. The fracture healing was repressed upon 6-OHDA treatment and rescued by VIP treatment. Micro-CT examination showed that the femoral bone micro-architecture at the fracture sites and mechanical properties were all impaired. Simultaneously, the expression level of osteogenic markers OCN and OPN were reduced in sympathectomized mice compared with vehicle group. While the VIP treatment rescued the repression effects of 6-OHDA on bone remodeling and significantly promoted bone quality and mechanical properties as well as increased osteogenesis marker expression in the sympathectomized mice. VIP administration promoted bone fracture healing by inhibiting bone resorption, making it a putative new alternative treatment strategy for fracture healing.
Identifiants
pubmed: 33999216
doi: 10.1007/s00223-021-00820-9
pii: 10.1007/s00223-021-00820-9
doi:
Substances chimiques
Vasoactive Intestinal Peptide
37221-79-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
55-65Subventions
Organisme : National Natural Science Foundation of China
ID : 81772322
Organisme : Hong Kong Government Research Grant Council, General Research Fund
ID : 14120118
Organisme : Hong Kong Government Research Grant Council, General Research Fund
ID : 14160917
Organisme : Hong Kong Government Research Grant Council, General Research Fund
ID : 9054014 N_CityU102/15
Organisme : Hong Kong Government Research Grant Council, General Research Fund
ID : C7030-18G
Organisme : Hong Kong Government Research Grant Council, General Research Fund
ID : T13-402/17-N
Organisme : Innovation and Technology Commission - Hong Kong
ID : PRP/050/19FX
Organisme : Hong Kong Innovation Technology Commission Funds
ID : ITS/448/18
Organisme : Hong Kong Medical Research Funds
ID : 16170951
Organisme : Hong Kong Medical Research Funds
ID : 17180831
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