Vasoactive Intestinal Peptide Stimulates Bone Marrow-Mesenchymal Stem Cells Osteogenesis Differentiation by Activating Wnt/β-Catenin Signaling Pathway and Promotes Rat Skull Defect Repair
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AbstractBone defect regeneration is a complex process that involves the coordination of a variety of different type of cells. As bone tissues are innervated and rich in nerve fibers, the neuropeptides released from various never fibers could regulate bone development, metabolism, and remodeling. Among all the neuropeptides, vasoactive intestinal peptide (VIP) could modulate the functions of both osteoblasts and osteoclasts, and may play a vital role in bone marrow mesenchymal stem cell (BMSC) osteogenesis during bone repair. In this study, we investigated the role of VIP in bone formation and the mechanisms of VIP in mediating BMSC osteogenic differentiation, and its possibility in clinical application of bone defect reconstruction. Our in vitro study results indicated that VIP promoted BMSC osteogenic differentiation by activating Wnt/β-catenin signaling pathway in BMSCs. VIP could also stimulate tube formation of EA.hy926 endothelial cell and increase vascular endothelial growth factor (VEGF) expression in BMSCs. Furthermore, in the rat skull defect model, VIP-conjugated functionalized hydrogel significantly enhanced cranial bone defect repair compared with the control group, with increased bone formation and angiogenesis. Taken together, as a member of neuropeptides, VIP could promote the BMSCs osteogenesis and angiogenesis differentiation in vitro and stimulate bone repair in vivo by activating Wnt/β-catenin signaling pathway. The knowledge obtained from this study emphasized the close association between innervation and bone repair process, and VIP may be a potential therapeutic agent for augmenting bone repair.
All Author(s) ListLiu Shi, Lu Feng, Mei-Ling Zhu, Zheng-Meng Yang, Tian-Yi Wu, Jia Xu, Yang Liu, Wei-Ping Lin, Jesica Hiu Tung Lo, Jinfang Zhang, Gang Li
Journal nameStem Cells and Development
Year2020
Month5
Volume Number29
Issue Number10
PublisherMary Ann Liebert, Inc
Pages655 - 666
ISSN1547-3287
eISSN1557-8534
LanguagesEnglish-United States
Keywordsbone defect repair, mesenchymal stem cells, osteogenesis

Last updated on 2020-15-10 at 00:28