The possible role of Gremlin1 in inflammatory apical periodontitis

Objective: In this study, we investigated the involvement of Gremlin1 on the pathological process of apical periodontitis and detect the underlying mechanisms preliminarily.Methods: Clinical healthy and inflamed periapical specimens were collected. Then, apical periodontitis (AP) animal models were established by consistent pulp exposure. In addition, AAV-shGremlin1 was injected into inflamed periapical lesions to inhibit the expression of Gremlin1. Alveolar bone loss was measured by Micro-CT. Furthermore, immunohistochemical or immunofluorescence staining of Gremlin1, phosphorylated-CREB, ICAM1, VCAM-1, IL-18 were performed.Results: The expression of Gremlin1 is markedly increased in periapical lesions not only in clinic samples but also in animal models. Moreover, in rats' AP model, we uncovered that the Gremlin1 protein expression levels in apical lesions is positively correlated with those of IL-18. Besides, the blockade of Gremlin1 in periapical lesions could substantially suppress the alveolar bone loss and restrains the inflammatory status by impacting the activation levels of phosphorylated-CREB, ICAM-1, VCAM-1, IL-18.Conclusions: Taken together, these results illustrated that Gremlin1 acts as a crucial mediator and possibly serves as a potential diagnostic marker for periapical periodontitis. Discovery of new factors involved in the pathophysiology of periapical periodontitis could contribute to the development of novel therapeutic treatment for the disease.

Automated summary

The study revealed that Gremlin1 expression levels are significantly increased in periapical lesions and may be positively correlated with IL-18 levels. Blocking Gremlin1 can significantly suppress bone resorption loss and restrain inflammatory status by affecting the activation levels of phosphorylated-CREB, ICAM-1, VCAM-1, IL-18.