Hertwig's epithelial root sheath (HERS) plays an important role in tooth root formation. In this study, we examined root formation of the first molar in mice, focusing on cell proliferation, cell death, cell migration, and the expression patterns of the signaling molecules, including glycoproteins and proteoglycans between PN8 and PN26. The number of HERS cells decreased during root formation, although HERS retained total length until PN15. The migration of HERS cells did not occur during root formation. Moreover, the immunopositive reaction of laminin beta-3 and syndecan-1 in HERS indicates that both cell adhesion and cell proliferation are essential for HERS development. Bmp-2, Bmp-4, and Msx-2 were expressed in HERS cells during root formation. We also developed an in vitro culture system for investigating the periodontium and suggest that this system provides an excellent vehicle for full exploration, and hence improved understanding, of the development and regeneration of the periodontium. Together, our results provide a comprehensive model describing the morphogenesis of early root development in vertebrates.

Apoptosis plays important roles in various stages of organogenesis. In this study, we hypothesized that apoptosis would play an important role in tooth morphogenesis. We examined the role of apoptosis in early tooth development by using a caspase inhibitor, z-VAD-fmk, concomitant with in vitro organ culture and tooth germ transplantation into the kidney capsule. Inhibition of apoptosis at the early cap stage did not disrupt the cell proliferation level when compared with controls. However, the macroscopic morphology of mice molar teeth exhibited dramatic alterations after the inhibition of apoptosis. Crown height was reduced, and mesiodistal diameter was increased in a concentration-dependent manner with z-VAD-fmk treatment. Overall, apoptosis in the enamel knot would be necessary for the proper formation of molar teeth, including appropriate shape and size.

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To cite this article: Kim TH, Kim JY, Mun HS, Lee HY, Roh YH, Uhm JS, Pak HN, Lee MH, Joung B. Heparin bridging in warfarin anticoagulation therapy initiation could increase bleeding in non-valvular atrial fibrillation patients: a multicenter propensity-matched analysis. J Thromb Haemost 2015; 13: 182-90.Summary. Background: The efficacy of heparin-bridging therapy during the initiation of oral anticoagulation therapy (OAC) in non-valvular atrial fibrillation (NVAF) is unclear. Objectives: To evaluate the efficacy and the safety of heparin-bridging therapy during OAC initiation in NVAF patients. Patients/Methods: This study included 5327 consecutive warfarin-na€ ıve NVAF patients who received OAC that was initiated with (n = 1053) or without (n = 4274) heparin bridging at four tertiary hospitals. Stroke and bleeding events within 30 days of OAC were evaluated. Results: While there was no difference in the incidence of stroke (0.5% vs. 0.3%, P = 0.381), major bleeding rate (0.9% vs. 0.3%, P = 0.004) was higher in heparin-bridged than in non-bridged patients. This trend remained in the propensity score-matched population (stroke 0.5% vs. 0.6%, P = 0.762; major bleeding 0.8% vs. 0.1%, P = 0.019). A high CHA 2 DS 2 -VASc score was an independent predictor for stroke, whereas bridging therapy had no beneficial effect in preventing stroke regardless of CHADS 2 or CHA 2 DS 2 -VASc scores. The HAS-BLED score had a predictive value for major bleeding (odds ratio 1.80, 95% confidence interval 1.11-2.92, P = 0.018), and heparin-bridging therapy was associated with a higher major bleeding rate (odds ratio 4.44, 95% confidence interval 1.68-11.72, P = 0.003), especially in patients with a HAS-BLED score of ≥ 1. Conclusions:The heparin-bridging therapy increased bleeding without the benefit of preventing stroke at the initiation of OAC in NVAF. Our data suggest that heparin bridging should not be considered at the initiation of OAC in NVAF patients.