Plasma membrane ion fluxes and NFAT-dependent gene transcription contribute to c-met-induced epithelial scattering.

Hepatocyte growth factor (HGF) signaling drives epithelial cells to scatter by breaking cell-cell adhesions and causing them to migrate as solitary cells, a process that parallels epithelial-mesenchymal transition. HGF binds and activates the c-met receptor tyrosine kinase, but downstream signaling required for scattering remains poorly defined. We have applied a chemical biology approach to identify components of HGF signaling that are required for scattering in an in vitro model system. This approach yields a number of small molecules that block HGF-induced scattering, including a calcium channel blocker. We show that HGF stimulation results in sudden and transient increases in ion channel influxes at the plasma membrane. Although multiple channels occur in the membranes of our model system, we find that TrpC6 is specifically required for HGF-induced scattering. We further demonstrate that HGF-induced ion influxes through TrpC6 channels coincide with a transient increase in nuclear factor of activated T-cells (NFAT)-dependent gene transcription and that NFAT-dependent gene transcription is required for HGF-induced cell scattering.

Pericoronal ostectomy: an alternative surgical technique for management of mandibular third molars in close proximity to the inferior alveolar nerve.

PURPOSE: Close proximity of the inferior alveolar nerve (IAN) to mandibular third molars (MTMs) may result in nerve injury during the extraction of third molars. Alternative surgical techniques, such as coronectomy, have been suggested to decrease this risk. This study examined a new alternative technique, the pericoronal ostectomy (PO), that is intended to decrease IAN injury in high-risk cases. PATIENTS AND METHODS: This prospective clinical cohort study consisted of 14 patients with 17 MTMs in close relation to the IAN. All patients were subjected to 2- and 3-dimensional preoperative radiographic evaluations. Selected patients with mesioangular and vertical bone impactions were treated by the staged PO technique. An institutional review board approval from the University of the Pacific was given to this study. RESULTS: Because of the PO procedure, all 17 high-risk MTMs in the study erupted to a more occlusal position away from the danger zone of the IAN and were eventually removed (mean distance of eruption, 2.0 mm). Three patients reported a transient neurosensory deficit, 2 with the IAN and 1 with a lingual nerve. All 3 had a full resolution of symptoms within 3 months of the postoperative period. CONCLUSION: The PO technique appears to be an additional viable alternative technique to extraction of MTMs in intimate proximity to the IAN.