Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic...

Nitric oxide (NO), which is synthesized by the enzyme NO synthase (NOS), is a versatile endogenous molecule with multiple biological effects on many tissues and organs. In dental pulp tissue, NO has been found to play multifaceted roles in regulating physiological activities, inflammation processes, and tissue repair events, such as cell proliferation, neuronal degeneration, angiogenesis, and odontoblastic differentiation. However, there is a deficiency of detailed discussion on the NO-mediated interactions between inflammation and reparative/regenerative responses in wounded dental pulp tissue, which is a central determinant of ultimate clinical outcomes. Thus, the purpose of this review is to outline the current molecular understanding on the roles of Janus-faced molecule NO in dental pulp physiology, inflammation, and reparative activities. Based on this knowledge, advanced physicochemical techniques designed to manipulate the therapeutic potential of NOS and NO production in endodontic regeneration procedures are further discussed. Impact statement The interaction between inflammation and reparative/regenerative responses is very important for regenerative endodontic procedures, which are biologically based approaches intended to replace damaged tissues. Inside dental pulp tissue, endogenous nitric oxide (NO) is generated mainly by immunocompetent cells and dental pulp cells and mediates not only inflammatory/immune activities but also signaling cascades that regulate tissue repair and reconstruction, indicating its involvement in both tissue destruction and regeneration. Thus, it is feasible that NO acts as one of the indicators and modulators in dental pulp repair or regeneration under physiological and pathological conditions.