Neuropeptide SP activates the WNT signal transduction pathway and enhances the proliferation of bone marrow stromal stem cells

Cell Biol Int. 2013 Nov;37(11):1225-32. doi: 10.1002/cbin.10158. Epub 2013 Aug 30.


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.

Keywords: BMSCs; SP; Wnt/β-catenin signalling; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Neurokinin-1 Receptor Antagonists / pharmacology
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Substance P / pharmacology*
  • Wnt Signaling Pathway / drug effects*


  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Neurokinin-1 Receptor Antagonists
  • Substance P