Traumatic compressive stress inhibits osteoblast differentiation through long chain non‐coding RNA Dancr

Abstract

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)-B 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-B signaling pathway. Results: Traumatic compressive stress inhibited the expressions of Alp, Runx2, and-Dancr 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-B signaling was activated after silencing Dancr, and the activated effect of traumatic force on NF-B signaling could be alleviated through overexpression of Dancr to some extent. Conclusion: Traumatic compressive stress can indirectly activate the NF-B signaling through downregulation of Dancr, thereby inhibiting osteogenic differentiation.

Unloading of occlusal force aggravates alveolar bone loss in periodontitis

“…Although traumatic occlusal force itself do not initiate PD, occlusal trauma could act as a cofactor to accelerate an existing plaque‐induced PD 9 . When it comes to the role of occlusion in periodontal disease, most of researches focused on the effects of traumatic occlusion, 9,30–32 while the role of physiological occlusal force remains largely unknown.…”

The Involvement of Long Non-Coding RNAs in Bone

“…Occlusal trauma, a pathological injury of periodontal tissue, stimulated the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) signaling, thus inhibiting the osteogenesis process. In this light, Lu et al [48] investigated the role and the underlying molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) in the inhibition of this process. The results showed that the traumatic compressive stressinduced inhibition of osteogenic differentiation is promoted by the activation of the NF-kB pathway through the downregulation of DANCR in MC3T3-E1 cells, while the induced overexpression of such lncRNA increases the expression of ALP and RUNX2 genes, thus alleviating the inhibitory effect induced by traumatic stress.…”

Compressive force‐induced LincRNA‐p21 inhibits mineralization of cementoblasts by impeding autophagy

“…LncRNAs regulate diverse cellular processes from normal development to disease progression 13 . Emerging studies have reported that lncRNAs participate in the regulation of different cells responding to environmental stress 5,14 . Lu et al reported that compressive force impeded the mineralization capability of osteoblasts by downregulating lncRNA Dancr expression 14 .…”

“…13 Emerging studies have reported that lncRNAs participate in the regulation of different cells responding to environmental stress. 5,14 Lu et al reported that compressive force impeded the mineralization capability of osteoblasts by downregulating lncRNA Dancr expression. 14 Our previous study found that 57 lncRNAs showed upregulated expression and 13 showed downregulated expression in cementoblasts subjected to mechanical stress, indicating that lncRNAs may be involved in mechanical compression-induced variations in cementoblast functions.…”

“…5,14 Lu et al reported that compressive force impeded the mineralization capability of osteoblasts by downregulating lncRNA Dancr expression. 14 Our previous study found that 57 lncRNAs showed upregulated expression and 13 showed downregulated expression in cementoblasts subjected to mechanical stress, indicating that lncRNAs may be involved in mechanical compression-induced variations in cementoblast functions. 5 LincRNA-p21, one of the lncRNAs with the strongest upregulation in expression, was identified as a transcriptional repressor of the p53-dependent apoptotic response 15 and was reported to regulate glycolytic metabolism.…”