Positive Correlation between Activated CypA/CD147 Signaling and MMP-9 Expression in Mice Inflammatory Periapical Lesion

AIM: Cyclophilin A (CypA)/CD147 signaling plays critical roles in the regulation of inflammation and bone metabolism. This study aimed to investigate the participation of CypA/CD147 in mice periapical lesions progression and its relationship with bone resorption. METHODOLOGY: Periapical lesions were induced by pulp exposure in the first lower molars of 40 C57BL/6J mice. The mice were sacrificed on days 0, 7, 14, 21, 28, 35, 42, and 49. Mandibles were harvested for X-ray imaging, microcomputed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. Western blot was employed to further detect the related molecular signaling pathways in LPS-stimulated RAW 264.7 cells treated with CypA inhibitor. RESULTS: The volume and area of the periapical lesions increased from day 0 to day 35 and remained comparably stable until day 49. Immunohistochemistry demonstrated that the CypA expression levels also increased from day 0 to day 35 and decreased until day 49, similar to CD147 expression (R(2) = 0.4423, P < 0.05), osteoclast number (R(2) = 0.5101, P < 0.01), and the expression of osteoclastogenesis-related matrix metalloproteinase 9 (MMP-9) (R(2) = 0.4715, P < 0.05). Serial sections further confirmed the colocalization of CypA and CD147 on osteoclasts with immunohistochemistry. And the distribution of CypA-positive or CD147-positive cells was positively correlated with the dynamics of MMP-9-positive cells by using immunofluorescence analysis. Furthermore, CD147 and MMP-9 expression in RAW 264.7 cells were both downregulated with CypA inhibitor treatment (P < 0.05). CONCLUSIONS: The present study reveals the positive correlation of CypA/CD147 signaling and osteoclast-related MMP-9 expression in mice inflammatory periapical lesions progression. Therefore, intervention of CypA/CD147 signaling could probably provide a potential therapeutic target for attenuating inflammatory bone resorption.