Project description:The association between T2 DM and BMSCs osteogenic differentiation has been documented in experimental settings. We examine miRNA expression specific for BMSCs from human jaw in Type 2 diabetics.
Project description:Osteoradionecrosis of the jaw (ORNJ) is a complication after head and neck radiotherapy that severely affects patients’ quality of life. Currently, an overall understanding of microenvironmental factors of ORNJ is still lacking. Here, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells with scRNA-Seq and the decrease of taurine in irradiated bone marrow mesenchymal stromal cells (BMSCs) with metabolomics. Compared to the unirradiated BMSCs, the taurine uptake of irradiated BMSCs increases. The taurine concentration in peripheral blood and jaws of irradiated mice are significantly lower than the unirradiated mice. Supplementation of taurine promotes osteogenic differentiation, decreases oxidative stress and DNA damage of irradiated BMSCs. Oral administration of taurine significantly promotes survival rate of irradiated mice and promotes osteogenesis of irradiated jaws. Our study sheds light on the role of taurine during the recovery of radiation-induced jaw injury, suggesting a potential non-invasive therapeutic means to combat ORNJ.
Project description:Analysis of gene expression in activation-tagged jaw-d mutant plants. Total RNA was extracted from the aerial parts of two weeks old jaw-d and control plants. Keywords: other
Project description:The jaws are complementary in form and function but develop asymmetrically, as the lower but not upper jaw bone forms around a prominent cartilage template. How such differences in skeletal composition are patterned is unclear. Here, we identify four Nuclear receptor 2f genes, nr2f1a, nr2f1b, nr2f2, and nr2f5, as enriched in zebrafish upper jaw precursors. Whereas loss of Nr2f genes results in expansion of upper jaw cartilage to resemble that of the lower jaw, Nr2f5 misexpression inhibits lower jaw cartilage formation. Genome-wide analyses show that Nr2f genes prevent expansion of lower jaw-associated gene expression into the upper jaw territory. Further, restriction of Nr2f expression by Endothelin1 signaling is critical for lower jaw development, as reducing Nr2f dosage fully restores lower jaw development in edn1 mutants. We propose that Nr2f genes drive jaw asymmetry by limiting early cartilage differentiation in the upper jaw to preserve more precursors for later osteogenesis.
Project description:Human diseases like oral cancer or injuries may cause irreversible substantial jaw defects. Axolotls are of special interest in regenerative maxillofacial research due to their unique ability to completely renew amputated jaws. Here we performed differential gene expression analyses based on RNA-seq for regenerating jaw tissue of the Mexican axolotl (Ambystoma mexicanum) to identify key players in this regenerative process. Within differentially expressed genes (p<0.001) we use enrichment and network analyses to identify increased expression of structural components crucial for tissue repair (Thbs3, Thbs4 and Col3a1) as well as for extracellular matrix structure (further collagens and Matn4). Genes of enzymatic function (AldoA, AldoC, Eno1, Ckm and Ak6) as well as muscle components (Atp2A1, Pvalb, Tpm3) are down-regulated. This first RNA-seq study on axolotl jaw tissue can help to elucidate the general molecular mechanisms underlying mandible regeneration and offer a chance for new regenerative strategies focusing on morphologically and functionally adequate replacement of these complex tissues.
Project description:Abstract Background: Bone marrow stromal cells (BMSCs) are being used for immune modulatory, anti-inflammatory and tissue engineering applications, but the properties responsible for these effects are not completely understood. Human BMSCs were characterized to identify factors that might be responsible for their clinical effects and biomarkers for assessing their quality. Methods: Early passage BMSCs prepared from marrow aspirates of 4 healthy subjects were compared to 3 human embryonic stem cell (hESC) samples, CD34+ cells from 3 healthy subjects and 3 fibroblast cell lines. The cells were analyzed with oligonucleotide expression microarrays with more than 35,000 probes. Results: BMSC gene expression signatures of BMSCs differed from those of hematopoietic stem cells (HSCs), hESCs and fibroblasts. Genes up-regulated in BMSCs were involved with cell movement, cell-to-cell signaling and interaction and proliferation. The BMSC up-regulated genes were most likely to belong to integrin signaling, integrin linked kinase (ILK) signaling, NFR2-mediated oxidative stress response, regulation of actin-based motility by Rho, actin cytoskeletal signaling, caveolar-mediated endocytosis, clathrin-mediated endocytosis and Wnt/beta catenin signaling pathways. Among the most highly up-regulated genes were structural extracellular (ECM) proteins: alpha1 and beta1 integrin chains, fibronectin, collagen type IIIalpha1, and collagen type Valpha1 and functional EMC proteins: connective tissue growth factor (CTGF) and transforming growth factor beta induced protein (TGFBI) and ADAM12. Conclusions: Global analysis of human BMSCs suggests that they are mobile, metabolically active, proliferative and interactive cells that make use of integrins and integrin signaling. They produce abundant ECM proteins; some of which may contribute to their clinical immune modulatory and anti-inflammatory effects. Seven samples from early passage BMSCs were prepared from marrow aspirates of healthy subjects and compared to 3 human embryonic stem cell (hESC) samples, CD34+ cells from 3 healthy subjects and 3 fibroblast cell lines. Total RNA from a pool of PBMCs from six healthy subjects was extracted and amplified into aRNA to serve as a reference.
Project description:The functional jaw is composed of multiple connective tissues including skeletal components (bone, cartilage, and teeth), tendon, ligament, and musculature. Cranial neural crest-derived mesenchyme of the mandibular arch give rise to diverse tissue types within the lower jaw. To understand how the specification of diverse cell types with spatial and temporal precision is achieved, we profile multi-omic chromatin accessibility (snATACseq) and transcriptome (snRNAseq) of jaw mesenchyme at single-cell resolution from the developing zebrafish jaw.