Overexpression of microRNA-141 inhibits osteoporosis in the jawbones of ovariectomized rats by regulating the Wnt/ß-catenin pathway.

OBJECTIVE: This work was aimed to investigate the effect of microRNA-141 (miR-141) overexpression in the jawbones of ovariectomized-induced osteoporosis rats and investigate the role of miR-141 in the Wnt/ß-catenin pathway. METHODS: Twenty-four female rats were randomly divided into the sham group, ovariectomized osteoporosis group (OP), miR-141 agonist group (miR-141), and miR-141 scramble group (Scramble). Bone mineral density (BMD) and pathological changes of the jaw were detected. Serum receptor activator of nuclear factor-B ligand (RANKL), osteoprotegerin, tartrate-resistant acid phosphatase (TRAP), and bone gla protein (BGP) levels were tested by ELISA. The expression of Runt-related transcription factor 2 (Runx2), and Osterix measured by immunohistochemistry and the expression of Wnt, ß-catenin, and Dickkopf1 (DKK1) proteins was measured by Western blot. Furhter, the Wnt agonist DKK2-C2, Wnt inhibitor Endostar were used to verify the effect of miR-141 overexpression on the Wnt/ß-catenin pathway. RESULT: Compared with the OP group, the content of osteoprotegerin increased while the levels of RANKL, BGP, TRAP decreased in the miR-141 and DKK2-C2 groups (p < 0.05). The levels of Runx2 and Osterix increased significantly in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). Interestingly, the protein expression of Wnt and ß-catenin increased while DKK1 was remarkably down-regulated in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). In contrast to the miR-141 group, the above results were reversed after treatment with the Endostar (p < 0.05). CONCLUSION: Overexpression of miR-141 could inhibit the osteoporosis of jawbones in ovariectomized rats by activating the Wnt/ß-catenin pathway.

CXC chemokine­7 inhibits growth and migration of oral tongue squamous cell carcinoma cells, mediated by the epithelial­mesenchymal transition signaling pathway.

Oral tongue squamous cell carcinoma (OTSCC) is the most common oral malignancy with different histopathological symptoms and etiology of tumorigenesis. Migration and invasion is the most important characteristics of OTSCC, and limits tumor therapy in clinics. The epithelial­to­mesenchymal transition (EMT) signaling pathway is an important process in the progress of tumor cell migration and invasion. Previous studies have indicated that C­X­C chemokine receptor­7 (CXCR­7) promotes the progression and metastasis of tumor cells, presenting a potential target molecule for cancer therapy. The present study investigated the inhibitory effects of C­X­C chemokine­7 (CXC­7) on human OTSCC cells both in vitro and in vivo. The results demonstrated that the Tca8113 human OTSCC cell line expressed higher levels of CXC­7 mRNA compared with the hNOE human normal oral epithelial cell line. MTT assays indicated that CXC­7 suppressed Tca8113 cell growth, and the cytotoxicity of CXC­7 was indicated as the cell survival of the negative control group was significantly decreased compared with the blank control and hNOE cells. Migration and invasion assays revealed that CXC­7 inhibited Tca8113 cell local expansion and distant metastasis. In addition, the results demonstrated that the extracellular signal­regulated kinase (ERK)/protein kinase B (AKT) signaling pathway was inhibited after CXC­7 treatment in Tca8113 cells. N­cadherin, E­Cadherin, Snail and Slug expression levels in the ERK/AKT signaling pathway were inhibited in Tca8113 cells after treatment with CXC­7. It was demonstrated that important extracellular matrix proteins involved in cell migration, including Slug, collagen type I and Vimentin, were significantly downregulated by CXC­7 treatment. In conclusion, CXC­7 inhibited growth and migration in OTSCC cells, mediated by the EMT signaling pathway. This suggests that CXC­7 serves an inhibitory role in OTSCC migration, implicating CXCR­7 as a promising biomarker for chemokine receptor­based drug development.

Low plasma levels of brain derived neurotrophic factor are potential risk factors for diabetic retinopathy in Chinese type 2 diabetic patients.

Previous studies suggested that neurotrophins play a role in the diabetic retinopathy (DR). We therefore evaluated the role of plasma brain derived neurotrophic factor (BDNF) levels in Chinese type 2 diabetic patients with and without diabetic retinopathy (DR). Plasma levels of BDNF were determined in type 2 diabetic patients (N=344). At baseline, the demographical and clinical data were taken. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic curves (ROC) was used to test the overall predict accuracy of BDNF and other markers. Diabetic patients with DR and vision-threatening diabetic retinopathy (VTDR) had significantly lower BDNF levels on admission (P<0.0001 both). BDNF improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.76 (95% confidence interval [CI], 0.71-0.82) to 0.89 (95% CI, 0.82-0.95; P<0.01) and for VDTR from 0.84 (95% CI, 0.78-0.92) to 0.95 (95% CI, 0.90-0.98; P<0.01). Multivariate logistic regression analysis adjusted for common risk factors showed that plasma BDNF levels≤12.4 ng/mL(1(rd) quartiles) was an independent marker of DR (OR=3.92; 95%CI: 2.31-6.56) and VTDR (OR=4.88; 95%CI: 2.21-9.30). The present study demonstrated that decreased plasma levels of BDNF were independent markers for DR and VDTR in Chinese type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.