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.

Role of neurotransmitter Substance P in progression of oral squamous cell carcinoma

“…SP is known to phosphorylate protein kinase Akt, which has antiapoptotic effects [18]. SP is also found to be involved in the proliferation of bone marrow stem cells via WNT signaling pathway [19] but it has to be studied in detail in the proliferation of tumor cells.…”

Neuropeptide substance P and the immune response

“…Human bone marrow mononuclear cells and fibroblasts also proliferate in response to substance P (Rameshwar et al, 2001b). Furthermore, it has been shown that SP could enhance proliferation of bone marrow stem cells (Mei et al, 2013). …”

Neuropeptide Substance P Improves Osteoblastic and Angiogenic Differentiation Capacity of Bone Marrow Stem CellsIn Vitro

“…To identify the first changes in the expression of BMP-2 and VEGF, observations were made on 1 day, 3 days, 5 days, and 7 days; these intervals were also employed to determine the effects of SP on the migration of the BMSCs. The concentration of SP (10 −8  mol/L) was chosen for the possible maximum effect [20]. …”

“…Additionally, the expression of osteoblastic genes and proteins is vital to bone generation [16], and Wnt signaling is an important regulatory factor in bone metabolism [17–19]. SP has been confirmed to exert a promoting effect on the proliferation and differentiation of BMSCs [20–24]. However, the effect of SP on BMP-2 expression is currently unclear.…”