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Dong Y.,Shandong University | Dong Y.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | Wu G.,Jinan Military General Hospital | Zhu T.,Shandong University | And 8 more authors.
Oncotarget | Year: 2017

Chronic sleep disturbance (CSD) has been linked to the development of temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis of TMJ-OA is unclear, recent studies indicate that osteochondral angiogenesis is important. We developed a rat model of CSD induced TMJ-OA to investigate the changes caused by sleep disturbance and to correlate them with vascular invasion in the TMJ. We found pathological alterations and an increased microvessel density in the rat TMJ following CSD. VEGF, Dll4 and p-ERK1/2, the expression of angiogenic factors, were highly expressed in the rat mandibular condylar cartilage and their expression increased with CSD. Furthermore, we show that VEGF-induce activation of ERK1/2, which in turn, increases Dll4 expression. Together, our results suggest that CSD can cause OA-like pathological alterations in the rat TMJ by increasing angiogenesis.


Shao S.,The Third Peoples Hospital Of Jinan | Li B.,The Third Peoples Hospital Of Jinan | Xue H.-M.,The Third Peoples Hospital Of Jinan | Huang H.-Y.,Shandong University | And 2 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

To evaluate the effects of alveolar ridge preservation with Bio-Oss bone substitute (Geistlich Pharma) on delayed implant osseointegration. The 3rd and 4th left and right mandibular premolars were extracted from four adult healthy male and female dogs. For the experimental group, we randomly selected two extraction sockets in each dog to be filled with Bio-Oss bone substitute (Geistlich Pharma). The two remaining extraction sockets remained untreated and served as the control group. Three months after Bio-Oss placement, dental implants were inserted into the alveolar bone of the experimental group and the control group. The osteogenic activity of the bone around the implants was assessed by evaluating the histological morphology and by estimating histomorphometric parameters at 3 and 6 months after delayed implantation. At 3 months, Goldner’s trichrome staining analysis showed that the bone-implant contact rate and mineralised bone area around the implant were significantly higher in the experimental group (75.98% ± 8.97% and 69.52% ± 9.63%, respectively) than in the control group (56.13% ± 8.18% and 52.82% ± 7.25%, respectively; P < 0.05). However, at 6 months, the two groups showed no significant difference. Fluorescence microscopy analysis revealed that the average mineralisation apposition rate of the bone tissue around the dental implant in the experimental group at 3 and 6 months was 6.80 ± 0.43 μm and 8.38 ± 0.84 μm, respectively, which was significantly higher than the rate in the control group (P < 0.05). These data indicated that alveolar ridge preservation by using Bio-Oss placement can promote osseointegration of delayed implantation. This may be a promising option for clinical use. © 2015, E-Century Publishing Corporation. All rights reserved.


Yang L.,Shandong University | Yang L.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | Yang L.,Yantai Stomatological Hospital | Wang T.,Yantai Stomatological Hospital | And 5 more authors.
Cancer Biomarkers | Year: 2016

BACKGROUND: BTB/POZ domain-containing protein 7 (BTBD7) is recognized as a regulatory gene that regulates epithelial cell dynamics and branching morphogenesis. It is also reported for regulating epithelial-mesenchymal transition (EMT) molecules and involved in the process of invasion and metastasis of lung cancer and hepatocellular carcinoma. Slug is a transcriptional factor of EMT which plays a crucial role in the process of primary salivary adenoid cystic carcinoma (SACC). However, the role of BTBD7 in SACC and the correlation with Slug have not been identified. This study investigated the expression of BTBD7 and correlation with Slug, as well as the prognostic significance of BTBD7 in SACC. METHODS: The expression of BTBD7 and Slug were examined in ACC-LM and ACC-83 cell lines and immunohistochemically in paraffin embedded tissue specimens from 66 primary SACC patients. Statistical analyses were performed to evaluate the correlation between BTBD7 expression and Slug expression and the prognostic significance of BTBD7 expression. RESULTS: BTBD7 protein expression was initially verified in ACC-LM and ACC-83 cell lines. The positive rate of BTBD7 expression was 62.1% in SACC to 20% in normal salivary tissues comparatively. BTBD7 expression was significantly correlated with Slug expression in SACC (P < 0.05). Increased BTBD7 expression was significantly associated with the TNM stage, tissue typing, distant metastasis and patients' poor clinical outcome. CONCLUSIONS: Positive expression of BTBD7 in SACC could play an important role in the development of cancer and may serve as a favorable predictor for diagnosis and poor prognosis of patients.


PubMed | Yantai Stomatological Hospital, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong University
Type: Journal Article | Journal: Cancer biomarkers : section A of Disease markers | Year: 2016

BTB/POZ domain-containing protein 7 (BTBD7) is recognized as a regulatory gene that regulates epithelial cell dynamics and branching morphogenesis. It is also reported for regulating epithelial-mesenchymal transition (EMT) molecules and involved in the process of invasion and metastasis of lung cancer and hepatocellular carcinoma. Slug is a transcriptional factor of EMT which plays a crucial role in the process of primary salivary adenoid cystic carcinoma (SACC). However, the role of BTBD7 in SACC and the correlation with Slug have not been identified. This study investigated the expression of BTBD7 and correlation with Slug, as well as the prognostic significance of BTBD7 in SACC.The expression of BTBD7 and Slug were examined in ACC-LM and ACC-83 cell lines and immunohistochemically in paraffin embedded tissue specimens from 66 primary SACC patients. Statistical analyses were performed to evaluate the correlation between BTBD7 expression and Slug expression and the prognostic significance of BTBD7 expression.BTBD7 protein expression was initially verified in ACC-LM and ACC-83 cell lines. The positive rate of BTBD7 expression was 62.1% in SACC to 20% in normal salivary tissues comparatively. BTBD7 expression was significantly correlated with Slug expression in SACC (P< 0.05). Increased BTBD7 expression was significantly associated with the TNM stage, tissue typing, distant metastasis and patients poor clinical outcome.Positive expression of BTBD7 in SACC could play an important role in the development of cancer and may serve as a favorable predictor for diagnosis and poor prognosis of patients.


Li Y.,Shandong University | Li Y.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | Guo H.,Shandong University | Guo H.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | And 6 more authors.
Archives of Oral Biology | Year: 2015

Objective: This study was conducted to investigate effects of coinfection of Porphyromonas gingivalis (P. gingivalis) or Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) with Fusobacterium nucleatum (F. nucleatum) on their adhering and invasive capacity to human gingival epithelial cells as well as the expression of interleukin-8 (IL-8) and human beta-defensin-2 (hBD-2) in human gingival epithelial cells. Design: P. gingivalis and A. actinomycetemcomitans were tested for their ability to attach and invade a human gingival epithelial cell line (Ca9-22) alone or coinfecting with F. nucleatum. Also, expression levels of IL-8 and hBD-2 were detected respectively using enzyme linked immunosorbent assay (ELISA) and real-time reverse transcription PCR (RT-PCR) when Ca9-22 cells were infected with P. gingivalis and A. actinomycetemcomitans alone or coinfecting with F. nucleatum. Results: F. nucleatum, P. gingivalis and A. actinomycetemcomitans were allowed to adhere and invade Ca9-22 cells, either each strain alone or under coinfection. The adhering and invasive abilities of P. gingivalis and A. actinomycetemcomitans were significantly greater when they were coincubated with F. nucleatum (P < 0.05) than either of them alone. These enhancements were inhibited by galactose. In addition, P. gingivalis and A. actinomycetemcomitans inhibited the activation of IL-8 and hBD-2 by F. nucleatum. Also, galactose disrupted this inhibition on the expression of IL-8 and hBD-2. Conclusion: These results suggested coinfection with F. nucleatum can enhance adhesion and invasion of P. gingivalis and A. actinomycetemcomitans to Ca9-22 cells, as well as inhibition on host innate immune response. © 2015 Elsevier Ltd. All rights reserved.


Wang L.,Shandong University | Wang L.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | Wu X.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | Wu X.,Laiwu City Peoples Hospital | And 10 more authors.
Oncology Reports | Year: 2016

The present study aimed to evaluate whether bromodomain 4 (BRD4) is expressed in Cal27 cells and to assess the effect of JQ1 on cell proliferation, apoptosis, invasion and BRD4, C-Myc and Twist expression in Cal27 cells. Immunofluorescence staining was used to determine whether BRD4 was expressed in Cal27 cells. Cell viability and proliferation were evaluated using CCK-8 assay. Flow cytometry was used to determine the apoptosis and cell cycle distribution. The cell invasion was evaluated using Transwell plate. The expression levels of BRD4, C-Myc and Twist were determined by quantitative RT-PCR (qRT-PCR) and western blotting. BRD4 was highly expressed in Cal27 cells. JQ1 inhibited cell proliferation, induced cell apoptosis, induced cell cycle arrest, and inhibited cell invasion. Gene and protein expression levels of BRD4, C-Myc and Twist were downregulated in cells treated with JQ1. JQ1 inhibited Cal27 cell growth and invasion, and downregulated expression of several oncogenes. JQ1 may be a new drug for oral squamous cell carcinoma treatment.


Yu X.-D.,Shandong University | Yu X.-D.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | Yang J.-L.,Dongying Peoples Hospital | Zhang W.-L.,Shandong University | And 2 more authors.
Tumor Biology | Year: 2015

The present study was performed to investigate the effect of resveratrol (trans-3,4′,5-trihydroxystilbene) present as a natural phytoalexin in grapes, peanuts, and red wine on oral squamous cancer cell lines, SCC-VII, SCC-25, and YD-38. MTS assay and flow cytometry, respectively, were used for the analysis of inhibition of cell proliferation and apoptosis. Western blot analysis was performed to examine the effect of resveratrol on the expression of proteins associated with cell cycle regulation. The results revealed a concentration- and time-dependent inhibition of proliferation in all the three tested cell lines on treatment with resveratrol. The IC50 of resveratrol for SCC-VII, SCC-25, and YD-38 cell lines was found to be 0.5, 0.7, and 1.0 μg/ml, respectively, after 48-h treatment. Examination of the cell cycle analysis showed that resveratrol treatment induced cell cycle arrest in the G2/M phase and enhanced the expression of phospho-cdc2 (Tyr 15), cyclin A2, and cyclin B1 in the oral squamous cell carcinoma (OSCC) cells. It also caused a marked increase in the percentage of apoptotic cells as revealed by the fluorescence-activated cell sorting analysis. Thus, resveratrol exhibits inhibitory effect on the proliferation of OSCC oral cancer cells through the induction of apoptosis and G2/M phase cell cycle arrest. © 2015 International Society of Oncology and BioMarkers (ISOBM)


Wei F.,Shandong University | Wei F.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | Yang S.,Shandong University | Yang S.,Shandong Provincial Key Laboratory of Oral Tissue Regeneration | And 11 more authors.
Mediators of Inflammation | Year: 2015

Orthodontic force may lead to cell damage, circulatory disturbances, and vascular changes of the dental pulp, which make a hypoxic environment in pulp. In order to maintain the homeostasis of dental pulp, hypoxia will inevitably induce the defensive reaction. However, this is a complex process and is regulated by numerous factors. In this study, we established an experimental animal model of orthodontic tooth movement to investigate the effects of mechanical force on the expression of VEGF and HIF-1α in dental pulp. Histological analysis of dental pulp and expressions of HIF-1α and VEGF proteins in dental pulp were examined. The results showed that inflammation and vascular changes happened in dental pulp tissue in different periods. Additionally, there were significant changes in the expression of HIF-1α and VEGF proteins under orthodontic force. After application of mechanical load, expression of HIF-1α and VEGF was markedly positive in 1, 3, 7 d, and 2 w groups, and then it weakened in 4 w group. These findings suggested that the expression of HIF-1α and VEGF was enhanced by mechanical force. HIF-1α and VEGF may play an important role in retaining the homeostasis of dental pulp during orthodontic tooth movement. © 2015 Fulan Wei et al.


PubMed | Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Laiwu City Peoples Hospital and Shandong University
Type: Journal Article | Journal: Oncology reports | Year: 2016

The present study aimed to evaluate whether bromodomain4 (BRD4) is expressed in Cal27 cells and to assess the effect of JQ1 on cell proliferation, apoptosis, invasion and BRD4, C-Myc and Twist expression in Cal27 cells. Immunofluorescence staining was used to determine whether BRD4 was expressed in Cal27 cells. Cell viability and proliferation were evaluated using CCK-8 assay. Flow cytometry was used to determine the apoptosis and cell cycle distribution. The cell invasion was evaluated using Transwell plate. The expression levels of BRD4, C-Myc and Twist were determined by quantitative RT-PCR (qRT-PCR) and western blotting. BRD4 was highly expressed in Cal27 cells. JQ1 inhibited cell proliferation, induced cell apoptosis, induced cell cycle arrest, and inhibited cell invasion. Gene and protein expression levels of BRD4, C-Myc and Twist were downregulated in cells treated with JQ1. JQ1 inhibited Cal27 cell growth and invasion, and downregulated expression of several oncogenes. JQ1 may be a new drug for oral squamous cell carcinoma treatment.

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