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

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.

Mycoplasma genitalium Protein of Adhesion Induces Inflammatory Cytokines via Cyclophilin A-CD147 Activating the ERK-NF-κB Pathway in Human Urothelial Cells

“…Notably, this study only demonstrated the in vitro production of inflammatory cytokines via the CypA/CD147/ERK/NF-κB pathway by SV-HUC-1 cells stimulated by rMgPa-induced eCypA. Reports have shown that the intervention of CypA/CD147 signaling could probably provide a potential therapeutic and drug target for mice inflammatory periapical lesions progression ( 40 ), Glioblastoma ( 41 ), APE ( 42 ), HCMV ( 43 ), and so on. This study did not investigate the mechanism of interaction between CypA and CD147, the elucidation of which warrants further detailed studies.…”

Cyclophilin A/CD147 Induces the Epithelial-to-mesenchymal Transition and Renal Fibrosis in Chronic Allograft Dysfunction by Regulating MAPK Signaling

“…Recent study has reported the positive relation of CyPA/CD147 signaling and osteoclast-related MMP-9 expression in mice in ammatory periapical lesions progression (18). Additionally, CyPA inhibitor NIM811 signi cantly reduced MMP-9 secretion during the differentiation process of foam cells, which also suggested the potential association of the CyPA/CD147 and MMP-9 expression.…”

“…Considering the important role of CD147 in the regulation of renal brosis, the CyPA binding to the CD147 was also noticed to be involved in the stimulation of renal brosis. Moreover, extracellular CyPA has been described to induce the chemotaxis of T cells, monocytes, and macrophages, which leads to the massive recruitment and in ltration of in ammatory cells in the renal allograft tissues (10,18). It is well known that certain pro-brotic cytokines could be produced and secreted during the in ammatory response, triggering the pathogenesis of organ brosis.…”

Novel long non‐coding RNA CYB561‐5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non‐small cell lung cancer

“…In this study, we predicted that Bsg may be an interacting protein of lnc‐CYB561‐5 and further confirmed this prediction by RNA pulldown and RIP assays in vitro. Bsg, also known as CD147, is expressed in a variety of cell types and is involved in the processes of organ development, wound healing, inflammation and tumour progression 37,38 . Recent studies show that Bsg is highly expressed in several cancer cell types and is associated with tumour size, tumour stage, progression and prognosis 39–41 .…”