PMID- 26707636 OWN - NLM STAT- MEDLINE DCOM- 20161221 LR - 20220330 IS - 1532-2785 (Electronic) IS - 0143-4179 (Linking) VI - 56 DP - 2016 Apr TI - Neuropeptide Y stimulates osteoblastic differentiation and VEGF expression of bone marrow mesenchymal stem cells related to canonical Wnt signaling activating in vitro. PG - 105-13 LID - S0143-4179(15)00228-0 [pii] LID - 10.1016/j.npep.2015.12.008 [doi] AB - Neuropeptide Y (NPY) is a neuropeptide secreted by sensory nerve fibers distributed in the marrow and vascular canals of bone tissue. However, the effect of NPY on the osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) remains controversial and has not been thoroughly investigated. To explore the osteogenic activity and the migration and VEGF expression capabilities of BMSCs affected by NPY, as well as the underlying mechanisms, we investigated the potential relationships among NPY, osteoblastic differentiation, angiogenesis and canonical Wnt signaling in BMSCs. NPY was observed to regulate osteoblastic differentiation at concentrations ranging from 10(-8) to 10(-12)mol/L, and the effects of NPY on the levels of Wnt signaling proteins were detected using Western blotting. To unravel the underlying mechanism, BMSCs were treated with NPY after pretreatment with the NPY-1R antagonist PD160170 or the Wnt pathway antagonist DKK1, and gene expression levels of Wnt signaling molecules and osteoblastic markers were determined by qPCR. Our results indicated that NPY significantly promoted osteoblastic differentiation of BMSCs in a concentration-dependent manner and up-regulated the expression levels of proteins including beta-catenin and p-GSK-3beta and the mRNA level of beta-catenin. Moreover, NPY promoted the translocation of beta-catenin into nucleus. The effects of NPY were inhibited by PD160170 or DKK1. Additionally, NPY enhanced the ability of BMSCs to migrate and promoted the expression of vascular endothelial growth factor (VEGF) as measured by immunocytochemical staining, qPCR and Western blot. These results suggested that NPY may stimulate osteoblastic differentiation via activating canonical Wnt signaling and enhance the angiogenic capacity of BMSCs. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Liu, Song AU - Liu S AD - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou City, Guangdong Province 510515, People's Republic of China. FAU - Jin, Dan AU - Jin D AD - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou City, Guangdong Province 510515, People's Republic of China. Electronic address: nfjindan@126.com. FAU - Wu, Jian-qun AU - Wu JQ AD - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou City, Guangdong Province 510515, People's Republic of China. FAU - Xu, Zi-yi AU - Xu ZY AD - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou City, Guangdong Province 510515, People's Republic of China. FAU - Fu, Su AU - Fu S AD - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou City, Guangdong Province 510515, People's Republic of China. FAU - Mei, Gang AU - Mei G AD - Department of Orthopaedics, Xiangyang Central Hospital, Xiangyang City, Hubei Province 441021, People's Republic of China. FAU - Zou, Zhen-Lv AU - Zou ZL AD - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou City, Guangdong Province 510515, People's Republic of China. FAU - Ma, Sheng-hui AU - Ma SH AD - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou City, Guangdong Province 510515, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151211 PL - Netherlands TA - Neuropeptides JT - Neuropeptides JID - 8103156 RN - 0 (Bmp2 protein, rat) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Neuropeptide Y) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, rat) SB - IM MH - Animals MH - Bone Morphogenetic Protein 2/metabolism MH - *Cell Differentiation/drug effects MH - Cell Movement/drug effects MH - Cells, Cultured MH - In Vitro Techniques MH - Male MH - Mesenchymal Stem Cells/drug effects/metabolism/*physiology MH - Neuropeptide Y/administration & dosage/*physiology MH - Osteoblasts/drug effects/*physiology MH - Rats MH - Vascular Endothelial Growth Factor A/*metabolism MH - Wnt Signaling Pathway/drug effects OTO - NOTNLM OT - BMSCs OT - Differentiation OT - Neuropeptide Y OT - VEGF OT - Wnt signaling EDAT- 2015/12/29 06:00 MHDA- 2016/12/22 06:00 CRDT- 2015/12/29 06:00 PHST- 2015/07/05 00:00 [received] PHST- 2015/12/09 00:00 [revised] PHST- 2015/12/10 00:00 [accepted] PHST- 2015/12/29 06:00 [entrez] PHST- 2015/12/29 06:00 [pubmed] PHST- 2016/12/22 06:00 [medline] AID - S0143-4179(15)00228-0 [pii] AID - 10.1016/j.npep.2015.12.008 [doi] PST - ppublish SO - Neuropeptides. 2016 Apr;56:105-13. doi: 10.1016/j.npep.2015.12.008. Epub 2015 Dec 11.