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

Autor: Xuan Li, Fa-Ming Chen, Xin-Yue Xu, Yi-Zhou Tan, Xiao-Tao He, Jia Wang, Yu Xia
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Agonist
Adult
Male
Cancer Research
Cell signaling
Periodontal ligament stem cells
Adolescent
Purinergic P2X Receptor Antagonists
medicine.drug_class
Periodontal Ligament
Cellular differentiation
Immunology
Interleukin-1beta
Inflammation
Article
Purinergic P2X Receptor Agonists
03 medical and health sciences
Cellular and Molecular Neuroscience
Transduction (genetics)
Young Adult
0302 clinical medicine
Adenosine Triphosphate
Osteogenesis
Acetamides
medicine
Humans
lcsh:QH573-671
Receptor
Periodontitis
Cells
Cultured
Chemistry
Tumor Necrosis Factor-alpha
lcsh:Cytology
Stem Cells
Cell Differentiation
Cell Biology
Middle Aged
Cell biology
030104 developmental biology
030220 oncology & carcinogenesis
Quinolines
Female
Receptors
Purinergic P2X7
Signal transduction
medicine.symptom
Zdroj: Cell Death and Disease, Vol 10, Iss 1, Pp 1-17 (2019)
Cell Death & Disease
ISSN: 2041-4889
DOI: 10.1038/s41419-018-1253-y
Popis: 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.
Databáze: OpenAIRE
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