dimethyloxalylglycine and 3-(5--hydroxymethyl-2--furyl)-1-benzylindazole

Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1α was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1α was not stabilised by tensile, but rather by compressive strain. HIF-1α stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1α destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1α. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1α via integrin mechanotransduction and downstream phosphorylation of kinases seems to be essential for the induction of VEGF, but not prostaglandin synthesis by PDLF during compressive (but not tensile) orthodontic strain.

Topics: Adolescent; Adult; Cells, Cultured; Female; Fibroblasts; Focal Adhesion Kinase 1; Genistein; Glycine; Glycosaminoglycans; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Indazoles; Integrins; Male; Mechanotransduction, Cellular; Periodontal Ligament; Phosphorylation; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Protein Stability; Signal Transduction; Stress, Mechanical; Tooth Movement Techniques; Urea; Vascular Endothelial Growth Factor A

The objective of this study was to determine the effect of light-emitting diode (LED) irradiation on the migration and proliferation of keratinocytes.. Keratinocytes play a key role in re-epithelialization during wound healing; it is speculated that low-level LED therapy might improve keratinocyte migration and proliferation.. Human keratinocyte cells (HKCs) were isolated from child or adult foreskins and irradiated with LED light with a wavelength of 640 nm and a dosage of 12 or 24 J/cm(2). Cell motility, migration, and proliferation were examined using live cell imaging, scratch assay, and a colorimetric cell counting assay, respectively. Hypoxia-inducible factor-1α (HIF-1α) protein levels were analyzed by using Western blotting. Filamentous actin (F-actin) was stained by phalloidin. YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzylindazole] was used as an HIF-1 inhibitor, and CoCl2 (cobalt chloride) and DMOG (dimethyloxaloyl glycine) are HIF-1α activators.. LED irradiation significantly promoted cell motility and migration, but did not significantly influence cell proliferation in HKCs. Furthermore, LED irradiation resulted in a reorganization of cellular F-actin and a dramatic upregulation of HIF-1α expression. Suppression of HIF-1α using the compound YC-1 prevented reorganization of the actin cytoskeleton following LED irradiation, suggesting that the effect of LED irradiation on the cytoskeleton is mediated through HIF-1α. Conversely, chemical activation of HIF-1α via DMOG or CoCl2 resulted in a reorganization of F-actin.. LED irradiation may increase keratinocyte migration via HIF-1α-dependent cytoskeletal reorganization.

Topics: Adult; Blotting, Western; Cell Movement; Cell Proliferation; Child; Cobalt; Cytoskeleton; Foreskin; Glycine; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Indazoles; Keratinocytes; Low-Level Light Therapy; Male; Up-Regulation