Trigeminal neurons control immune-bone cell interactions and metabolism in apical periodontitis
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ABSTRACT: Apical periodontitis (AP) is an inflammatory disease occurring following tooth infection with distinct osteolytic activity. Despite increasing evidence that sensory neurons participate in regulation of non-neuronal cells, their role in the development of AP is largely unknown. We hypothesized that Nav1.8+ nociceptors regulate bone metabolism changes in response to AP. Methods: A selective ablation of nociceptive neurons in Nav1.8Cre/ DTALox mouse line was used to evaluate the development and progression of AP using murine model of infection-induced AP. Micro-computed tomography examination was applied to quantify osteolytic lesions following induction of AP. Additionally, RT-PCR, RNAscope, and immunohistochemical (IHC) analysis were used to investigate the expression of immune cells, osteoblasts, and osteoclasts. Co-culture of trigeminal ganglia (TG) neurons from DTALox (control) and Nav1.8Cre/ DTALox mice with either IDG-SW3 or MC3T3-E1 osteoblast precursor cell lines or RAW264.7 murine macrophages were used to assess osteoblast and osteoclast function, by RNA sequencing, mineralization, and osteoclastic assays. Results: Ablation of Nav1.8+ nociceptors had earlier progression of AP with larger osteolytic lesions compared to the controls. IHC and RNAscope analysis demonstrated greater number of macrophages, T-cells, osteoclast and osteoblast precursors as well as an increased RANKL:OPG ratio at earlier time points among Nav1.8Cre/ DTALox mice. There was an increased expression of IL-1a and IL-6 within lesions of nociceptor-ablated mice. Further, co-culture experiments demonstrated that TG neurons promoted osteoblast mineralization and inhibited osteoclastic function. Conclusion: The findings suggest that TG Nav1.8+ neurons contribute to modulation of the AP development by delaying the influx of immune cells, promoting osteoblastic differentiation, and decreasing osteoclastic activities. This newly uncovered mechanism could become a therapeutic strategy for the treatment of AP and minimize the persistence of osteolytic lesions in refractory cases.
ORGANISM(S): Mus musculus
PROVIDER: GSE198091 | GEO | 2022/09/01
REPOSITORIES: GEO
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