The Role of the IL-33/ST2 Axis in Periapical Lesion Progression

Objectives: It is believed that IL-33/ST2 axis is implicated with the breakdown of osteoclast and osteoblast activity balance. The aim of this study was to evaluate the role of IL-33/ST2 axis in the development and progression of experimentally induced periapical lesions in mice.
Methods: Periapical lesions were induced in first molars of WT and ST2 knockout (KO) mice. Samples were collected at 7, 10 and 14 days of the lesion for the following analyses: analysis of IL-33 and ST2 expression; determination of periapical lesions area by histology and volume by computed microtomography (μCT); osteogenic and osteoclastogenic markers expression by q-PCR; neutrophil quantification by myeloperoxidase activity.
Results: IL-33 showed to be increased at the lesion site compared to control at 14 days. The time course analysis showed increased expression of ST2 in periapical lesion compared to control at day 10 and 14. Histological images showed that WT mice exhibited significantly larger periapical lesion area compared to control group at 7 days (p<0.05) and at 14 days (p<0.05). On the other hand, the lesion size of ST2KO was not significantly different comparing 7 days and 14 days. μCT image analysis showed the same pattern of lesion development. A smaller number of neutrophils in ST2KO group were observed compared to WT mice, when evaluated at 7 days of lesion (p<0.05). Runx2 expression in ST2KO was higher in lesion site compared to control side, at 14 days. The markers related to bone resorption, cathepsin K and MMP-9, were significantly abrogated in the lesion site of ST2KO mice, at 14 days (p<0.05).
Conclusions: We concluded that in ST2KO mice, the lesion was less extensive and osteoclasts less functioning. It all suggests that the IL-33/ST2 pathway play an important role in osteoclasts activation and periapical lesion development.