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Introduction: CCN1 is an immediate-early gene product pivotal for arthritis progression. We have previously shown that sirtuin 6 (SIRT6) inhibited hypoxia-induced CCN1 expression in osteoblasts. Herein we examined the contribution of cyclic AMP-responsive element binding protein (CREB)/CRE to this suppressive action and the influence of CCN1 on cyclooxygenase (COX) 2 synthesis. Materials and methods: MC3T3-E1 murine osteoblasts were cultured under normoxia (21% oxygen) or hypoxia (2% oxygen). Expressions of CCN1, phospho-CREB (Ser133), COX2 and relevant kinases were assessed by Western blot. SIRT6 was overexpressed in cultured osteoblasts and arthritic joints by a lentiviral-based technique. Activities of CCN1 gene promoter constructs were examined by luciferase reporter assay. Interaction between CREB and CCN1 promoter was assessed by chromatin immunoprecipitation (ChIP). Collagen-induced arthritis (CIA) was established in 20 rats to evaluate the effects of SIRT6 therapy on osteoblastic expressions of phospho-CREB, CCN1 and COX2. Results: SIRT6 suppressed hypoxia-enhanced CCN1 expression and CREB phosphorylation. Attenuation of calcium/calmodulin-dependent protein kinase II (CaMKII) may be responsible for SIRT6-induced CREB inhibition. CRE at − 286 bp upstream of the ATG start codon was essential for CCN1 expression under hypoxia and SIRT6 reduced hypoxia-stimulated CREB/CRE interaction. Forced expression of CREB rescued SIRT6-suppressed CCN1 synthesis. CCN1 induced COX2 expression in osteoblasts. In rat CIA, the therapeutic effect of SIRT6 was accompanied by decreases in osteoblastic expressions of phospho-CREB, CCN1 and COX2. Conclusion: Our study indicated that the benefits of SIRT6 to inflammatory arthritis and bone resorption are at least partially derived from its modulation of CREB/CCN1/COX2 pathway in osteoblasts. [ABSTRACT FROM AUTHOR]

Background: The current study aimed to compare the measurements of the mandible morphology using 3D cone beam computed tomography (CBCT) images with those using 2D CBCT-synthesized cephalograms; to quantify errors in measurements based on 2D synthesized cephalograms; and to clarify the effects such errors have on the description of the mandibular growth.Methods: Mandibles of six miniature pigs were scanned monthly using CBCT over 12 months and the data were used to reconstruct the 3D bone models. Five anatomical landmarks were identified on each bone model, and the inter-marker distances and monthly distance changes were calculated and taken as the gold standard. Synthetic 2D cephalograms were also generated for each bone model using a digitally reconstructed radiography (DRR)-generation method. Errors in cephalogram measurements were determined as the differences between the calculated variables in cephalograms and the gold standard. The variations between cephalograms and the gold standard were also compared using paired t-tests.Results: While the inter-marker distance increases varied among the marker pairs, all marker pairs increased their inter-marker distances gradually every month, reaching 50% of the total annual increases during the fourth and fifth months, and then slowing down in the subsequent months. The 2D measurements significantly underestimated most of the inter-marker distances throughout the monitoring period, in most of the monthly inter-marker distance changes during the first four months, and in the total growth (p < 0.05).Conclusions: Significant errors exist in the measurements using 2D synthesized cephalogram, underestimating the mandibular dimensions and their monthly changes in the early stages of growth, as well as the total annual growth. These results should be considered in dental treatment planning at the beginning of the treatment in order to control more precisely the treatment process and outcome. [ABSTRACT FROM AUTHOR]