ABSTRACT
Abstract Objective: To investigate the involvement of IL-6/STAT3 signaling pathway activation in macrophage polarization and bone destruction related to apical periodontitis (AP) stimulated by Porphyromonas gingivalis. Methodology: Macrophage polarization, IL-6/STAT3 expression, and the presence of P. gingivalis were detected in human AP tissues via RT-qPCR, western blotting, and immunohistochemistry staining. Murine bone marrow derived macrophages were isolated and cultured with P. gingivalis W83 in vitro, and levels of macrophage IL-6 expression, STAT3 phosphorylation, and macrophage polarization with or without the selective STAT3 phosphorylation inhibitor Stattic (5 μM) were detected via ELISA, western blotting, RT-qPCR, and flow cytometry, respectively. P. gingivalis-induced murine AP models were constructed, and bone destruction and macrophage polarization in the apical region were evaluated. Transwell co-culture systems were used to investigate the effects of macrophages infected with P. gingivalis on osteogenesis and osteoclastogenesis. Results: P. gingivalis was detected in human AP tissues that highly expressed IL-6/STAT3, and the M1 subtype of macrophages was more abundant in these tissues. P. gingivalis infection induced IL-6 expression, STAT3 phosphorylation, and M1 polarization of macrophages, while 5 μM of Stattic partially abolished these activation effects. Systemic STAT3 blockade via oral administration of Stattic at a dose of 25 mg kg-1 alleviated murine periapical bone resorption and apical infiltration of M1 macrophages induced by P. gingivalis infection in vivo. Furthermore, macrophages infected with P. gingivalis promoted bone destruction via secretion of IL-6, TNF-α, and RANKL, which hinder pre-osteoblast expression of Runx2 and accelerate pre-osteoclast expression of NFAT2. Conclusions: The activation of IL-6/STAT3 signaling pathway is involved in mediating macrophages M1 polarization in the P. gingivalis induced apical inflammatory context and may also be intimately involved in the bone loss caused by P. gingivalis infection, directing the M1 macrophage infiltration during the progression of AP.
ABSTRACT
Objective@#To investigate the diagnosis, treatment and prognosis of nonodontogenic periapical lesions and to provide a reference for clinical diagnosis and treatment.@*Methods@# A case of a patient with right upper molar pulp with apical penetration and local occlusion admitted to the West China Stomatological Hospital of Sichuan University was retrospectively analyzed, and the curative effect of microapical surgery and pith preservation was also analyzed.@*Results @#The imaging features of tooth 16 showed periradicular radiolucency combined with local radiopaque lesions around the distal buccal apical area. Endodontic microsurgery was performed under local anesthesia. Soft tissue coverage was observed in the distal buccal apical area during the surgery, and no radiopaque tissue was detected. The distal buccal root apex was cut by 3 mm, and mineral trioxide aggregate was used for root-end backfilling. The postoperative pathological results revealed fibrous connective tissue. One-week recall X-ray examination showed tight root-end backfilling and no periradicular radiolucency; an electrical test of pulp vitality showed positive results. The four-year follow-up showed that there was no discoloration in tooth 16 and no significant difference in thermal and electrical tests of pulp vitality compared with control teeth. Combining the clinical manifestations, imaging features, surgical exploration results and pathological reports, the case was most likely to be cemental hypoplasia. Through the literature review, the treatment and healthy pulp preservation of such cases by endodontic microsurgery under the premise of preserving teeth has not been reported.@*Conclusion@#For maxillary posterior teeth with periapical lesions but healthy pulp, accurate estimation of pulp status, endodontic microsurgical exploration and application of bioactive materials can achieve vital pulp preservation while removing the lesions.