Differential regulation of NPY and SP receptor expression in STRO‐1+ve PDLSCs by inflammatory cytokines

• Published in: Journal of periodontal research 2022-01, Vol.57 (1), p.186-194, Article 186
• Main Authors: Winning, Lewis, El Karim, Ikhlas A., Linden, Gerard J., Irwin, Christopher R., Killough, Simon A., Lundy, Fionnuala T.
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cytokines; Gene Expression; Humans; Immunomagnetic separation; Inflammation; Interleukin 1; neurogenic inflammation; Neuropeptide receptors; Neuropeptide Y; Neuropeptide Y - genetics; Neuropeptides; osteoblastic differentiation; Osteogenesis; Periodontal Ligament; periodontal ligament stem cells; Periodontitis; Receptors, Neurokinin-1 - metabolism; Receptors, Neuropeptide Y - metabolism; Stem Cells; Substance P; Tachykinin; Tachykinin receptors; Tumor necrosis factor; Tumors
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/jre.12952

Objectives The aims of this study were to investigate neuropeptide receptor expression regulation on STRO‐1 +ve periodontal ligament stem cells (PDLSCs) in response to inflammatory cytokines and to investigate a potential osteogenic effect of neuropeptides. Background Nerve fibres innervating the periodontal tissues in humans contain several neuropeptides including neuropeptide Y and substance P. The role of neuropeptide receptors on PDLSCs, including their response to the local inflammatory environment of periodontitis, is currently unknown. Methods A homogenous population of STRO‐1 +ve PDLSCs was prepared by immunomagnetic separation of cells obtained by the tissue out‐growth method from healthy premolar teeth from a single donor. Regulation of gene expression of the neuropeptide Y Y1 receptor and substance P receptor tachykinin receptor 1 was investigated. A potential osteogenic effect of neuropeptide Y and substance P was also investigated by measuring alkaline phosphatase (ALP) activity, Alizarin red staining and quantifying osteogenic gene expression. Results Treatment of STRO‐1 +ve PDLSCs with tumour necrosis factor‐alpha or interleukin 1‐beta up‐regulated the expression of the neuropeptide Y’s Y1 receptor, but down‐regulated substance P’s receptor. Significantly increased ALP activity was observed in STRO‐1 +ve PDLSCs treated with neuropeptide Y but not substance P. Further studies showed that neuropeptide Y had a modest osteogenic effect on cells at both a functional level and a gene level. Conclusions Expression of the neuropeptide Y Y1 receptor gene on STRO‐1 +ve PDLSCs was sensitive to local inflammatory cytokines. Treatment of cells with neuropeptide Y was found to produce a modest enhanced osteogenic effect.