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Background: Occlusal trauma is an important local contributing factor aggravating periodontal pocket and alveolar bone absorption in periodontal diseases. Our previous studies have found that occlusal trauma inhibited osteogenic differentiation through nuclear factor (NF)-κB signaling. To further investigate the underlying mechanism, the aim of this study was to explore the role of long chain non-coding differentiation antagonizing non-protein coding RNA (Dancr) in the inhibitory effect of traumatic stress on osteoblast differentiation.Methods: We took the MC3T3-E1 cells as object in vitro research and stimulated cells with simple stress load, Dancr-siRNA + stress load, Dancr overexpression-plasmid + stress load. Quantitative real-time polymerase chain reaction was used to detect the RNA expression levels of Dancr, alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2). The protein expressions of Alp and Runx2 were tested by Western blot and the activity of Alp was qualitatively demonstrated by Alp staining. In addition, Western blot was performed to investigate the role of Dancr in affecting NF-κB signaling pathway.Results: Traumatic compressive stress inhibited the expressions of Alp, Runx2, andDancr in MC3T3-E1 cells. Stress-induced inhibition of osteoblast differentiation was promoted after silencing Dancr. Overexpression of Dancr could alleviate the inhibitory effect of traumatic force on osteoblast differentiation to some extent. Furthermore, NF-κB signaling was activated after silencing Dancr, and the activated effect of traumatic force on NF-κB signaling could be alleviated through overexpression of Dancr to some extent.Conclusion: Traumatic compressive stress can indirectly activate the NF-κB signaling through downregulation of Dancr, thereby inhibiting osteogenic differentiation. [ABSTRACT FROM AUTHOR]

Background: Occlusal trauma is an important factor promoting bone loss caused by periodontal diseases. Although there are reports of traumatic force promoting bone resorption in periodontal diseases, no studies examining the inhibition of bone formation by traumatic force and the underlying mechanism have been reported. The aim of this study was to investigate the mechanism whereby traumatic force inhibits bone formation.Methods: MC3T3-E1 cells were induced to undergo osteogenic differentiation and subjected to cyclic uniaxial compressive stress with or without stimulation with Pg. LPS. The expression of osteoblast markers and the activation of IKK-NF-κB signaling were evaluated in vitro. Then, MC3T3-E1 cells were induced to undergo osteogenic differentiation and subjected to cyclic uniaxial compressive stress with or without IKK-2 Inhibitor VI. The expression of osteoblast markers was determined. Then, the classic Wnt signaling pathway (β-catenin, Gsk3β, p-Gsk3β, and Dkk1) was further evaluated in vitro. Finally, occlusal trauma was induced in Wistar rats with or without the injection of IKK-2 Inhibitor VI, to evaluate changes in bone mass and IKK-NF-κB and Wnt/β-catenin signaling in vivo.Results: After stimulation with Pg. LPS and traumatic force, IKK-NF-κB signaling was significantly activated in vitro. The expression of osteoblast markers and the activity of alkaline phosphatase in MC3T3-E1 cells declined after traumatic force loading and were rescued when IKK-NF-κB signaling was blocked. Wnt/β-catenin signaling was accordingly inhibited upon force loading, but this inhibition was reversed when IKK-NF-κB was antagonized in vitro. X-ray and Micro-CT analysis of the mandibles of the rats as well as HE and TRAP staining showed that bone loss induced by occlusal trauma declined after IKK-NF-κB was inhibited. The expression of p65 and IκBα was increased when occlusal trauma was induced in Wistar rats, whereas β-catenin, OCN, and Runx2 levels were decreased. After blocking IKK-NF-κB, significant upregulation of β-catenin, OCN, and Runx2 was observed in rats suffering from occlusal trauma.Conclusions: IKK-NF-κB signaling could be activated by traumatic force or occlusal trauma. Its activation promoted the degradation of β-catenin, ultimately inhibiting osteogenic differentiation in vitro and bone formation in vivo. [ABSTRACT FROM AUTHOR]