High levels of HIF-1ɑ in hypoxic dental pulps associated with teeth with severe periodontitis.

In this study we investigated the expression of HIF-1ɑ in dental pulps of the teeth with severe periodontitis. The expression of HIF-1ɑ in dental pulps of the teeth with severe periodontitis was detected by immunohistochemistry, immunofluorescence and real-time PCR. Bone marrow macrophages (BMMs) were cultured under hypoxia in vitro. HIF-1ɑ, osteoclast-specific factors (NFATc1, CTSK and c-fos) and RANKL-induced osteoclastogenesis were evaluated by immunofluorescence, TRAP staining and western blotting. High levels of HIF-1ɑ protein were detected in dental pulps of teeth with severe periodontitis, whereas few positive HIF-1ɑ expressions were detected in healthy dental pulps. Hypoxia occurred in the dental pulps in response to heavy periodontitis. Many HIF-1ɑ-positive infiltratory inflammatory cells were observed around blood vessels. Tooth internal resorption was found in some teeth with severe periodontitis. The HIF-1ɑ levels were upregulated in BMMs under hypoxia, which also promoted osteoclast formation and resorption by NFATc1, CTSK and c-fos. Teeth with severe periodontitis show hypoxic dental pulps and increased potential of osteoclastic differentiation.

Isorhamnetin 3-O-neohesperidoside promotes the resorption of crown-covered bone during tooth eruption by osteoclastogenesis.

Delayed resorption of crown-covered bone is a critical cause of delayed tooth eruption. Traditional herbal medicines may be good auxiliary treatments to promote the resorption of crown-covered bone. This study was carried out to analyse the effect of isorhamnetin 3-O-neohesperidoside on receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis in vitro and resorption of the crown-covered bone of the lower first molars in mice in vivo. Isorhamnetin 3-O-neohesperidoside promoted osteoclastogenesis and the bone resorption of mouse bone marrow macrophages (BMMs) and upregulated mRNA expression of the osteoclast-specific genes cathepsin K (CTSK), vacuolar-type H + -ATPase d2(V-ATPase d2), tartrate resistant acid phosphatase (TRAP) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). NFATc1, p38 and AKT signalling was obviously activated by isorhamnetin 3-O-neohesperidoside in osteoclastogenesis. Isorhamnetin 3-O-neohesperidoside aggravated resorption of crown-covered bone in vivo. In brief, isorhamnetin 3-O-neohesperidoside might be a candidate adjuvant therapy for delayed intraosseous eruption.

Long non-coding RNA NEAT1 promotes migration and invasion of oral squamous cell carcinoma cells by sponging microRNA-365.

Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to serve key roles in numerous human cancer types, but its function in oral squamous cell carcinoma (OSCC) and underlying regulatory mechanism have not been evaluated. The present study demonstrated that expression of NEAT1 was significantly higher in OSCC tissue and cell lines compared with adjacent non-tumour tissue and normal oral keratinocytes, respectively. Additionally, upregulation of NEAT1 was significantly associated with advanced clinical stage and shorter survival time in patients with OSCC. Bioinformatics analysis and luciferase reporter gene assay data confirmed the interaction between NEAT1 and miR-365, and it was revealed that NEAT1 may downregulate microRNA (miR)-365 expression in OSCC cells. Furthermore, inhibition of NEAT1 expression led to a significant reduction in OSCC cell migration and invasion, which was accompanied by reduced matrix metalloproteinase (MMP)-2 and MMP9 protein expression. By contrast, inhibition of miR-365 eliminated suppressive effects of NEAT1 knockdown on OSCC cell migration and invasion. miR-365 was significantly downregulated in OSCC tissue and cell lines and an inverse correlation between miR-365 and NEAT1 expression in OSCC tissue was observed. To conclude, the present study demonstrated that NEAT1 promoted migration and invasiveness of OSCC cells by sponging miR-365. The current study suggests that NEAT1 may serve as a novel therapeutic target for the treatment of OSCC.