Abstract
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.
Highlights
Periapical lesions, which occur as a result of bacterial infection of the dental pulp, are osteolytic bone defects characterized with the host response-mediated inflammation and alveolar bone destruction [1,2,3]
Cyclophilin A (CypA)/CD147 complex is a regulator of inflammatory responses which strongly induces the migration of monocytes/macrophages and promotes the secretion of
Recent studies confirmed that CypA/CD147 complex functions in inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and atherosclerosis [10, 20, 23]
Summary
Periapical lesions, which occur as a result of bacterial infection of the dental pulp, are osteolytic bone defects characterized with the host response-mediated inflammation and alveolar bone destruction [1,2,3]. The local inflammatory reaction is involved in the recruitment of various inflammatory cells and secretion of cytokines, including matrix metalloproteinases (MMPs), IL-1β, and IL-6, thereby resulting in osteoclast formation and alveolar bone resorption [4,5,6]. Osteoclasts are the exclusive cells engaged in cartilage and alveolar bone degrading, playing critical roles in pathological bone destruction [7, 8]. The specific mechanism of osteoclast-mediated bone resorption in periapical lesion is not fully elucidated. High CypA expression is detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and the gingival crevicular fluid of patients
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