title: Neuropeptide SP activates the WNT signal transduction pathway and enhances the proliferation of bone marrow stromal stem cells.
abstract: Substance P (SP) mediates multiple activities in various cell types, such as proliferation, anti-apoptotic response, and inflammation. We have investigated the effects of SP, NK1 antagonist and DKK1 on proliferation of bone marrow stromal stem cells (BMSCs), as well as the underlying mechanism. Isolated BMSCs were exposed to SP (10(-8)  M) (group A), SP + NK1 antagonist (1 µM) (group B), SP + DKK1 (0.2 µg/mL) (group C), or the same amount of PBS (group D). Expression of gene and protein of Wnt/β-catenin signalling was detected using quantitative PCR and western blotting. SP (10(-8)  M) significantly enhanced the proliferation of BMSCs and the number of viable cells was reduced by treatment with NK1 antagonist (1 µM) or DKK1 (0.2 µg/mL). SP also significantly increased the expression of C-myc mRNA, Lef1, β-catenin protein and C-myc protein, but decreased the expression of Tcf7 and p-β-catenin protein compared to group D. These roles of SP were inhibited by the NK1 antagonist and DKK1. Expression of CyclinD1 and β-catenin mRNAs, however, was not significantly influenced by SP, NK1 antagonist and DKK1. These findings suggest that SP enhances BMSC proliferation via regulation of the Wnt/β-catenin signalling pathway.
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Mei
authors.forename: Liheng
authors.initials: L
authors.lastname: Xia
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Tuo
authors.forename: Su
authors.initials: S
authors.lastname: Fu
authors.forename: Zhenlv
authors.initials: Z
authors.lastname: Zou
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Jin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P
keywords: BMSCs; SP; Wnt/β-catenin signalling; proliferation