Journal of advanced research · 2026
Periodontitis accelerates STING-mediated bone remodeling during orthodontic tooth movement.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Jin Yuqin, Ren Jiangyan, Li Baochao, Li Jialing, Yu Xuanxuan, Wang Yanyi, He Shumin, Liu Chao, Ding Liang, Li Huang
Аннотация
INTRODUCTION: Orthodontic tooth movement (OTM) is a mechanically induced inflammatory process. Intriguingly, OTM under periodontitis conditions orchestrates a complex inflammatory microenvironment and exacerbates bone resorption.
OBJECTIVES: Stimulator of interferon genes (STING) is a key inflammation mediator, but its role in OTM with periodontitis was unclear.
METHODS: We established an OTM model in rats with ligature-induced periodontitis. In vitro, rat periodontal ligament fibroblasts (PDLFs) were subjected to compressive stress and LPS to mimic orthodontic force and periodontitis inflammation. STING was activated with agonists (cGAMP/diABZI) or inhibited with H151 or knockdown. Inflammatory responses and bone resorption were assessed. RNA sequencing and co-IP followed by LC-MS/MS were used to identify downstream signals.
RESULTS: STING activation in PDLFs increased IL-1β and IL-6 while reducing Runx-2 and osteogenesis. In periodontitis-OTM rats, STING, IL-1β and IL-6 were upregulated and Runx-2 downregulated on the compression side, leading to increased alveolar bone loss that was rescued by H151. Under mechanical-inflammatory stress, activated STING triggered ER stress, and a cascade of cellular responses including increased pro-inflammatory mediators, enhanced apoptosis, altered mechano-response, and suppressed osteogenesis. Meanwhile, Annexin A2 (Anxa2) was identified as a novel STING interactor. Anxa2 knockdown mirrored STING inhibition, suppressing ER stress, inflammatory activation, apoptosis and mechano-response. Mechanistically, Anxa2 knockdown markedly reduced P65 phosphorylation and nuclear translocation, suggesting Anxa2 may serve as an intermediary linking STING to NF-κB activation. STING-Anxa2 interaction was notably increased in PDLFs and in compression-side periodontal tissues under mechanical-inflammatory stress.
CONCLUSIONS: Within an inflammatory milieu, STING activation in PDLFs is associated with ER stress, pro-inflammatory responses, apoptosis, and suppressed osteogenesis that collectively accelerate bone resorption during OTM. We identified Annexin A2 (Anxa2) as a novel STING interactor whose knockdown attenuated these responses and NF-κB activation, suggesting Anxa2 as a functional intermediary in STING-mediated inflammation.
OBJECTIVES: Stimulator of interferon genes (STING) is a key inflammation mediator, but its role in OTM with periodontitis was unclear.
METHODS: We established an OTM model in rats with ligature-induced periodontitis. In vitro, rat periodontal ligament fibroblasts (PDLFs) were subjected to compressive stress and LPS to mimic orthodontic force and periodontitis inflammation. STING was activated with agonists (cGAMP/diABZI) or inhibited with H151 or knockdown. Inflammatory responses and bone resorption were assessed. RNA sequencing and co-IP followed by LC-MS/MS were used to identify downstream signals.
RESULTS: STING activation in PDLFs increased IL-1β and IL-6 while reducing Runx-2 and osteogenesis. In periodontitis-OTM rats, STING, IL-1β and IL-6 were upregulated and Runx-2 downregulated on the compression side, leading to increased alveolar bone loss that was rescued by H151. Under mechanical-inflammatory stress, activated STING triggered ER stress, and a cascade of cellular responses including increased pro-inflammatory mediators, enhanced apoptosis, altered mechano-response, and suppressed osteogenesis. Meanwhile, Annexin A2 (Anxa2) was identified as a novel STING interactor. Anxa2 knockdown mirrored STING inhibition, suppressing ER stress, inflammatory activation, apoptosis and mechano-response. Mechanistically, Anxa2 knockdown markedly reduced P65 phosphorylation and nuclear translocation, suggesting Anxa2 may serve as an intermediary linking STING to NF-κB activation. STING-Anxa2 interaction was notably increased in PDLFs and in compression-side periodontal tissues under mechanical-inflammatory stress.
CONCLUSIONS: Within an inflammatory milieu, STING activation in PDLFs is associated with ER stress, pro-inflammatory responses, apoptosis, and suppressed osteogenesis that collectively accelerate bone resorption during OTM. We identified Annexin A2 (Anxa2) as a novel STING interactor whose knockdown attenuated these responses and NF-κB activation, suggesting Anxa2 as a functional intermediary in STING-mediated inflammation.