RETRACTED ARTICLE: Role of the P2X7 receptor in inflammation-mediated changes in the osteogenesis of periodontal ligament stem cells

Abstract

Accumulating evidence indicates that the pluripotency of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions; however, the underlying mechanisms remain largely unexplored. In this study, we hypothesize that the P2X7 receptor (P2X7R) is a key molecule linked to inflammation-associated impairment of PDLSCs. We first investigated P2X7R expression in PDLSCs under normal and inflammatory conditions and then determined the effect of a P2X7R agonist (BzATP) or antagonist (BBG) on PDLSC osteogenesis under various conditions. Gene-modified PDLSCs were used to further examine the role of P2X7R and the signaling pathway underlying P2X7R-enhanced osteogenesis. We found that inflammatory conditions decreased P2X7R expression in PDLSCs and reduced osteogenesis in these cells. In addition, activation of P2X7R by BzATP or overexpression of P2X7R via gene transduction reversed the inflammation-mediated decrease in PDLSC osteogenic differentiation. When selected osteogenesis-related signaling molecules were screened, the PI3K-AKT-mTOR pathway was identified as potentially involved in P2X7R-enhanced PDLSC osteogenesis. Our data reveal a crucial role for P2X7R in PDLSC osteogenesis under inflammatory conditions, suggesting a new therapeutic target to reverse or rescue inflammation-mediated changes in PDLSCs for future mainstream therapeutic uses.

mTOR‐mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP

“…Interestingly, activation of P2X 7 receptors also contributes to the increased lactic acid output and upregulated key glycolytic enzymes and transporters to promote the “Warburg effects” in cancer cells, suggesting a close connection between P2X 7 and glycolysis (Amoroso, Falzoni, Adinolfi, Ferrari, & Di Virgilio, ). It is noteworthy that all three receptors are able to activate the PI3K‐Akt pathway, an important upstream regulator for mTOR (H. Q. Li et al, ; Moore, Hunter, & Hers, ; Xu et al, ). It is likely that activation of P2Y 12 , P2Y 4 , and P2X 7 receptors combinatorically contribute to mTOR activation and glycolytic induction by ATP.…”

“…It is noteworthy that all three receptors are able to activate the PI3K-Akt pathway, an important upstream regulator for mTOR (H. Q. Li et al, 2013;Moore, Hunter, & Hers, 2014;Xu et al, 2019). It is likely that activation of P2Y 12 , P2Y 4 , and P2X 7 receptors combinatorically contribute to mTOR activation and (Zhao et al, 2018).…”

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

“…Western blot assays were performed to measure the exosome surface markers CD9, CD63, CD81 and Alix on M0-Exos, M1-Exos and M2-Exos. The exact procedures of the Western blot assay were previously described (Xu et al, 2019). The primary antibodies used in this study were anti-mouse CD63 antibody (Abcam, Cambridge, UK), anti-mouse CD81 antibody (Cell Signaling Technology, Danvers, MA, USA), anti-mouse CD9 antibody (Abcam, Cambridge, UK) and anti-mouse Alix antibody (Cell Signaling Technology, Danvers, MA, USA).…”

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

“…Given that the Wnt/β-catenin, Akt, TGF-β/Smad, BMP/Smad, and MAPK pathways have been demonstrated to regulate the osteogenesis/cementogenesis process [20][21][22][23][24][25][26][27][28], key genes involved in the above pathways were selected to screen the potential pathways that regulate M2 Mφ-enhanced cementoblastic differentiation. When the expression of the selected genes in CM-M2-treated PDLSCs (M2 group) and untreated PDLSCs (Control group) was analyzed using qRT-PCR, the pathway-related genes that were differentially expressed between the two groups were plotted in a heatmap (Fig.…”