Vasoactive Intestinal Peptide Stimulates Bone Marrow-Mesenchymal Stem Cells Osteogenesis Differentiation by Activating Wnt/β-Catenin Signaling Pathway and Promotes Rat Skull Defect Repair

被引：70

作者：

Shi, Liu ^{[1
,2
,3
]}

Feng, Lu ^{[1
]}

Zhu, Mei-Ling ^{[1
]}

Yang, Zheng-Meng ^{[1
]}

Wu, Tian-Yi ^{[1
,4
]}

Xu, Jia ^{[1
]}

Liu, Yang ^{[1
]}

Lin, Wei-Ping ^{[1
]}

Lo, Jessica Hiu Tung ^{[1
]}

Zhang, Jin-Fang ^{[1
,5
]}

Li, Gang ^{[1
,6
]}

机构：

[1] Univ Hong Kong, Prince Wales Hosp, Fac Med,Shatin, Dept Orthopaed & Traumatol,Li Ka Shing Inst Hlth, Room 74038,5F Lui Chee Woo Clin Sci Bldg, Hong Kong, Peoples R China

[2] Southeast Univ, Zhongda Hosp, Trauma Ctr, Sch Med, Nanjing, Peoples R China

[3] Southeast Univ, Sch Med, Nanjing, Peoples R China

[4] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Orthopaed Surg, Shanghai, Peoples R China

[5] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Lingnan Med Res Ctr, Guangzhou, Peoples R China

[6] Chinese Univ Hong Kong, CUHK ACC Space Med Ctr Hlth Maintenance Musculosk, Shenzhen Res Inst, Shenzhen, Peoples R China

来源：

STEM CELLS AND DEVELOPMENT | 2020年 / 29卷 / 10期

基金：

中国国家自然科学基金;

关键词：

vasoactive intestinal peptide; mesenchymal stem cells; osteogenesis; bone defect repair; ALKALINE-PHOSPHATASE; CHONDROCYTE DIFFERENTIATION; HYALURONIC-ACID; TNF-ALPHA; IN-VITRO; EXPRESSION; OSTEOBLAST; VIP; MINERALIZATION; PROLIFERATION;

D O I：

10.1089/scd.2019.0148

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Bone 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/beta-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/beta-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.

引用

页码：655 / 666

页数：12

共 58 条

[1]

Aranda E, 2009, BIOL RES, V42, P377, DOI /S0716-97602009000300012

[2] Effect of donor characteristics, technique of harvesting and in vitro processing on culturing of human marrow stroma cells for tissue engineered growth of bone [J].