Mouse Nuclear factor kB ELISA Kit

Objectives Mesenchymal stem cell (MSC)-based dental tissue regeneration is a potential treatment method in future, while inflammation and hypoxia niche will affect MSC-mediated tissue regeneration. In this research, we intended to investigate the influence and mechanism of secreted frizzled-related protein 2(SFRP2) on MSC function under inflammation and hypoxia conditions. Material and methods Stem cells from apical papilla (SCAPs) were used in this study. The alkaline phosphatase (ALP) activity, Alizarin Red S staining, scratch-simulated wound migration and transwell chemotaxis assay were used to evaluate the functions of SFRP2. The Western blot, real-time RT-PCR and ChIP assays were used to evaluate the mechanism of SFRP2. Results Under inflammation and hypoxia conditions, the over-expression of SFRP2 could enhance the osteo/odontogenic differentiation ability. Mechanismly, SFRP2 inhibited canonical Wnt/beta-catenin signalling pathway and then inhibited the target genes of nuclear factor kappa B (NFkB) signalling pathway. Inflammation or hypoxia conditions could promote the expression of lysine demethylase 2A (KDM2A) and repress SFRP2 transcription through decreasing histone methylation in the SFRP2 promoter. Besides, proteomic analysis showed that SFRP2 promoted SCAPs to secret more functional cytokines, which improve the migration, chemotaxis and osteo/odontogenic ability of MSCs. Conclusions Our discoveries revealed that SFRP2 enhanced the osteo/odontogenic differentiation and paracrine potentials of SCAPs under hypoxia and inflammation conditions and provided a potential cytokine for promoting tissue regeneration in hypoxia and inflammatory niche.

Although salivary gland cancers comprise only 3-6% of head and neck cancers, treatment options for patients with advanced-stage disease are limited. Because of their rarity, salivary gland malignancies are understudied compared to other exocrine tissue cancers. The comparative lack of progress in this cancer field is particularly evident when it comes to our incomplete understanding of the key molecular signals that are causal for the development and/or progression of salivary gland cancers. Using a novel conditional transgenic mouse (K5:RANKL), we demonstrate that Receptor Activator of NFkB Ligand (RANKL) targeted to cytokeratin 5-positive basal epithelial cells of the salivary gland causes aggressive tumorigenesis within a short period of RANKL exposure. Genome-wide transcriptomic analysis reveals that RANKL markedly increases the expression levels of numerous gene families involved in cellular proliferation, migration, and intra- and extra-tumoral communication. Importantly, cross-species comparison of the K5:RANKL transcriptomic dataset with The Cancer Genome Atlas cancer signatures reveals the strongest molecular similarity with cancer subtypes of the human head and neck squamous cell carcinoma. These studies not only provide a much needed transcriptomic resource to mine for novel molecular targets for therapy and/or diagnosis but validates the K5:RANKL transgenic as a preclinical model to further investigate the in vivo oncogenic role of RANKL signaling in salivary gland tumorigenesis.