Elevated Matrix Metalloproteinase-9 Expression Correlates With Advanced Stages of Oral Cancer and Is Linked to Poor Clinical Outcomes.

PURPOSE: Using a meta-analytic approach, the relation between increased matrix metalloproteinase-9 (MMP-9) expression, tumor stage, and clinical outcomes in oral cancers was investigated. MATERIALS AND METHODS: Multiple English- and Chinese-language electronic databases were searched to identify high-quality case-and-control studies relevant to this meta-analysis. Methodologic quality of the included trials was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement to ensure consistency in reviewing and reporting the results. Statistical analyses were carried out with STATA 12.0 statistical software. RESULTS: Nine case-and-control studies containing a combined total of 419 patients with oral cancer were included in the present meta-analysis. Results showed that patients who were positive for MMP-9 expression had a significantly poorer overall survival compared with those negative for MMP-9 (effect size = 2.10; 95% confidence interval, 0.98 to 3.22; P < .001). MMP-9 expression also positively correlated with lymph node metastasis and advanced T-stage groups (P < .05 for all comparisons). Further, high MMP-9 expression level correlated with increased oral cancer risk in Asians (P < .05 for all comparisons) as shown by method-stratified subgroup analysis. CONCLUSION: The present results strongly suggest that MMP-9 expression level influences tumor invasion and metastasis in oral cancers. Based on these results, MMP-9 can be an excellent therapeutic target in patients with oral cancer.

[Clinical application of midpiece facial nerve dissection in regional parotidectomy].

OBJECTIVE: To propose and evaluate the clinical effect of midpiece facial nerve dissection through transparotid approach in regional parotidectomy. METHODS: A total of 136 patients with benign parotid tumors were categorized into three groups according to the way of facial nerve dissection: anterograde dissection from main trunk (anterograde, n=70), retrograde dissection from distal branches (retrograde, n=34), and midpiece dissection through transparotid approach (middle dissection, n=32). Surgery duration, facial nerve injury, salivary fistula, earlobe sensation, Frey's syndrome, and aesthetic evaluation were compared. RESULTS: The surgery duration in the middle dissection group was significantly shorter than that in the other two groups. The proportion of salivary fistula was higher in the anterograde group (9 cases, 12.9%; P<0.05) compared with that in the other groups. Postoperative facial nerve injury was similar between the middle dissection (1 case, 3.1%) and anterograde groups (3 cases, 4.3%) with lower injury rate compared with the retrograde group (7 cases, 20.6%). The anterograde group had more cases of hypoesthesia of the earlobe (12 cases, 17.1%; P<0.05) than the other two groups. Aesthetic score was higher in the anterograde and middle dissection groups compared with that in the retrograde group (P<0.05). CONCLUSIONS: Midpiece facial nerve dissection is technically feasible and clinically viable in regional parotidectomy.

Effects of rhBMP-2 gene transfection to periodontal ligament cells on osteogenesis.

The present study aims to investigate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteogenesis of periodontal ligament (PDL) cells. The expression vector of rhBMP-2 (pcDNA3.1-rhBMP-2) was established. PDL cells were obtained through the enzymatic digestion and tissue explant methods and verified by immunohistochemistry. Cells were classified into experimental (cells transfected with pcDNA3.1/rhBMP-2-EGFP), blank (cells with no transfection) and control group (cells transfected with empty plasmid). rhBMP-2 expression was assessed via Western blotting analysis. The mineralization ability, alkaline phosphatase (ALP) activity and level of related osteogenic biomarkers were detected to evaluate the osteogenic characteristics of PDL cells. The rhBMP-2 expression vector (pcDNA3.1-rhBMP-2) was successfully established. Primary PDL cells displayed a star or long, spindle shape. The cultured cells were long, spindle-shaped, had a plump cell body and homogeneous cytoplasm and the ellipse nucleus contained two or three nucleoli. Cells displayed a radial, sheaf-like or eddy-like arrangement after adherence growth. Immunohistochemical staining confirmed that cells originated from mesenchymal opposed to epithelium. The experimental group exhibited an enhanced mineralization ability, higher ALP activity and increased expression of rhBMP-2 and osteogenic biomarkers (Runx2, collagen type I and osteocalcin) than the blank and control group. The present study demonstrated that rhBMP-2 transfection enhances the osteogenesis of PDL cells and provides a possibility for the application of rhBMP-2 expression products in dental disease treatment.

IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway.

Periodontal ligament stem cells (PDLSCs) are tissue-specific mesenchymal stem cells (MSCs), having an important role in regenerative therapy for teeth loss. Interleukin-7 (IL-7) is a key cytokine produced by stromal cells including MSCs, and exhibits specific roles for B and T cell development and osteoblasts differentiation of multiple myeloma. However, the effect of IL-7 on osteogenic differentiation of PDLSCs remains unclear. Therefore, in the present study we determined whether IL-7 affects the proliferation and osteogenic differentiation of PDLSCs in vitro and explored the associated signaling pathways for IL-7-mediated cell differentiation. The results demonstrated that the isolated human PDLSCs possessed MSCs features, highly expressing CD90, CD44, CD105, CD29 and CD73, and almost did not expressed CD34, CD45, CD11b, CD14 and CD117. IL-7 could not significantly affect the proliferation of PDLSCs, but it decreased their osteogenic differentiation and inhibited alkaline phosphatase (ALP) activity. The results of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting exhibited that the expression levels of Runx-2, SP7 and osteocalcin (OCN) were significantly reduced by IL-7. Further studies indicated that IL-7 did not significantly change JNK, ERK1/2 and p38 protein production, but markedly suppressed their phosphorylation levels. These data suggest that IL-7 inhibits the osteogenic differentiation of PDLSCs probably via inactivation of mitogen-activated protein kinase (MAPK) signaling pathway.

Tormentic acid inhibits LPS-induced inflammatory response in human gingival fibroblasts via inhibition of TLR4-mediated NF-κB and MAPK signalling pathway.

OBJECTIVE: Periodontal disease is one of the most prevalent oral diseases, which is associated with inflammation of the tooth-supporting tissues. Tormentic acid (TA), a triterpene isolated from Rosa rugosa, has been reported to exert anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of TA on lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs). METHODS: The levels of inflammatory cytokines such as interleukin (IL)-6 and chemokines such as IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), IκBα, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) was determined by Western blotting. RESULTS: The results showed that Porphyromonas gingivalis LPS significantly upregulated the expression of IL-6 and IL-8. TA inhibited the LPS-induced production of IL-6 and IL-8 in a dose-dependent manner. Furthermore, TA inhibited LPS-induced TLR4 expression; NF-κB activation; IκBα degradation; and phosphorylation of ERK, JNK, and P38. CONCLUSION: TA inhibits the LPS-induced inflammatory response in HGFs by suppressing the TLR4-mediated NF-κB and mitogen-activated protein kinase (MAPK) signalling pathway.