Basic ResearchBacteria-reactive Immune Response May Induce RANKL-expressing T Cells in the Mouse Periapical Bone Loss Lesion
Section snippets
Animals
C57BL/6j mice (8-week-old males) were kept in the Forsyth Animal Facility. The experimental protocols used in this study were approved by the Forsyth Institutional Animal Care and Use Committee.
Induction of Periapical Lesion
Periapical lesions were induced by pulp exposure of the mandibular first molar pulps of mice (n = 5/group) following the protocol published previously (15). Both sides of mandibular first molars were exposed using a ¼-size dental round bur. Three groups of animals receiving pulp exposure were sacrificed
Pulp Exposure Induces Inflammatory Tissue Disruption in Periapical Lesions
On day 3 after pulp exposure, the periodontal ligament space at the apex of teeth was enlarged (Fig. 1B) compared with control healthy tissue (Fig. 1A). Newly formed blood vessels were also observed in the periapical lesion (Fig. 1B), indicating the induction of the primary inflammatory response by pulp exposure. At day 7, remarkable inflammatory cell infiltration was observed in the periapical lesion (Fig. 1C). Furthermore, substantial bone resorption was found at the apical area at day 14 (
Discussion
This study showed that CD3+ T cells produce RANKL in the periapical lesion with resulting pathogenic bone resorption. The infiltration of RANKL-expressing CD3+ T cells in the periapical lesion peaked between days 3 and 7, whereas such infiltration remitted to baseline by day 14 after pulp exposure. The inflammatory cell infiltration in the lesion occurring within the first 3 days after pulp exposure appears to be composed of innate immune cells (Fig. 1B), some of which, probably macrophages,
Conclusion
Specific bacterial invasion into root canals activates an adaptive immune response, which results in the induction of RANKL-producing, bacteria-specific memory T cells, possibly contributing to osteoclast-mediated bone resorption in the periapical lesion.
Acknowledgments
The authors deny any conflicts of interest related to this study.
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2017, Journal of EndodonticsCitation Excerpt :In line with these reports, our results showed secretions of IL-6 and TNF-α were decreased by uPAR siRNA under inflammatory conditions, indicating its proinflammatory role in HPDLF inflammation. RANKL, an important mediator in the activation of osteoclasts, has been reported to be highly associated with alveolar bone resorption in rat periapical lesions (32, 33). Recent studies showed miR-335-5p positively regulates MSC chondrogenesis and osteogenesis, whereas others demonstrated miR-335-5p inhibits both adipogenic and osteogenic differentiation of MSCs and abolishes the in vivo chondro-osseous potential of hMSCs (13, 15, 16, 34).