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.
Highlights
Periodontitis is one of the most common infectious diseases, and the resulting destruction of tooth-supporting tissues is the main reason for tooth loss in adults[1]
Under inflammatory culture conditions, the level of P2X7 receptor (P2X7R) mRNA in periodontal ligament stem cells (PDLSCs) was significantly decreased compared with that under normal conditions (p < 0.05)
To determine the effect of P2X7R gene transduction on osteogenesis under inflammatory conditions, we evaluated the osteogenesis of gene-modified cells in response to exposure to inflammatory factors or a P2X7R antagonist (BBG)
Summary
Periodontitis is one of the most common infectious diseases, and the resulting destruction of tooth-supporting tissues is the main reason for tooth loss in adults[1]. Given the crucial role of the periodontium, the aim of periodontal therapy is to prevent infection and retard/prevent disease progression and to regenerate damaged periodontal tissue and/or reconstruct lost tooth-supporting structures, Official journal of the Cell Death Differentiation Association. Xu et al Cell Death and Disease (2019)10:20 findings from the preclinical stage to the clinical stage has largely been attributed to changes in the regenerative potential of stem cells in various in vivo situations[7,8]. Despite the robust functionality exhibited by stem cells in artificially created bone defects in animal models, predictable tissue regeneration is not achieved when they are applied to treat periodontitis-caused tissue loss, at least in part because these cells may be functionally compromised in an inflammatory environment[6]. An effective strategy for modulating PDLSCs in a chronic inflammatory environment toward correct differentiation and proper function has far been an unrealized goal[19]
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