Positive Correlation between Activated CypACD147 Signaling and MMP-9 Expression in Mice Inflammatory Periapical Lesion

Abstract EN

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 (R2 = 0.4423, P < 0.05), osteoclast number (R2 = 0.5101, P < 0.01), and the expression of osteoclastogenesis-related matrix metalloproteinase 9 (MMP-9) (R2 = 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.