CXCL12-CXCR4/CXCR7 Axis Modulates Foreign Body Response around Titanium Implant

doi:10.13701/j.cnki.kqyxyj.2025.03.010

Abstract

Abstract: Objective: To investigate the regulatory role of C-X-C motif ligand 12 (CXCL12)-C-X-C chemokine receptor type 4/7 (CXCR4/7) axis in the foreign body response (FBR) around titanium implants. Methods: The effects of polymethyl methacrylate (PMMA) and titanium (Ti) on the expression of CXCR4 and CXCR7 of macrophages were detected by flow cytometry. Besides, macrophage typing and the expression of related inflammatory cytokines were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and flow cytometry. Animal models of implant foreign body reaction were constructed. The experimental animals were divided into four groups: the titanium implant group, the titanium implant group injected with AMD3100, the PMMA implant group, and the PMMA implant with simvastatin (Sim) injection. Then, the expression of CXCL12-CXCR4/CXCR7 pathway, the function of macrophages, and the foreign body reaction around the implant were detected by immunohistochemical staining, immunofluorescence staining, and HE staining. Results: In vitro experiments showed that titanium promoted the increase of CXCR4 expression and the decrease of CXCR7 expression on macrophages, and the transformation of macrophages into anti-inflammatory types. Immunohistochemical staining showed that CXCR4 was highly expressed and CXCR7 was low around Ti implant, while the PMMA group was opposite. Immunofluorescence staining of macrophages showed that the number of anti-inflammatory M2 macrophages in the titanium group was significantly higher than that in the PMMA group at all time points, and HE staining showed that the FBR in the titanium group was mild. When CXCR4 antagonists or CXCR7 antagonists were added, respectively, the peri-implant conditions of titanium and PMMA implants were reversed. Conclusion: The CXCRL12-CXCR4/7 axis can be a new target for regulating the FBR around titanium implants.

Key words: foreign body response, macrophage, CXCR4, CXCR7

YU Siyi, CAI Xinjie, HUANG Cui. CXCL12-CXCR4/CXCR7 Axis Modulates Foreign Body Response around Titanium Implant[J]. Journal of Oral Science Research, 2025, 41(3): 229-237.

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