Impact of Cellular Senescence on the Immune-Inflammatory Response and Regenerative Capacity of Human Dental Pulp...

Cellular senescence is a state of irreversible cell cycle arrest that can compromise tissue homeostasis through the secretion of inflammatory mediators and disruption of the cellular microenvironment. In dental pulp, senescence may impair reparative functions and increase susceptibility to inflammation and degeneration. However, the specific effects of senescence on the immune behavior of pulp cells remain poorly understood. This study aimed to investigate how senescence influences the viability, morphology, migration, proliferation, and immune response of human dental pulp cells.

Cellular senescence was induced with 500 μM doxorubicin and confirmed by β-galactosidase staining. To simulate immunoinflammatory conditions, cells were stimulated with lipopolysaccharide, either alone or in combination with interferon-gamma. Morphologic changes were analyzed by scanning electron microscopy, while cell viability and proliferation were assessed using the Trypan Blue exclusion assay. Migratory capacity was evaluated through the scratch wound healing assay. Gene expression of pro- and anti-inflammatory mediators was quantified by real-time polymerase chain reaction.

The results of this study indicate that cellular senescence impairs the dental pulp's essential functions, particularly its regenerative and repair capacity under inflammatory conditions. Senescent pulp cells exhibited reduced viability, proliferation, and migration, along with morphologic changes suggesting decreased tissue function. Inflammatory pathways were altered, showing increased proinflammatory cytokine expression and decreased regenerative cytokine expression.

The findings suggest that senescence can directly impact the prognosis of conservative endodontic treatments, particularly in patients with pulp compromised by lesions. This emphasizes the need for therapeutic strategies to mitigate senescence effects and preserve pulp vitality.