Effects of occlusal rest design on pressure distribution beneath the denture base of a distal extension removable partial denture-an in vivo study.

This study aimed to investigate the pressure distribution beneath the denture bases of removable partial dentures (RPDs) with different occlusal rest designs (ORDs) by in vivo measurement. Four types of detachable occlusal rests (mesial and distal, distal, mesial, and nonrest) were placed on the direct abutment teeth of distal extension RPDs in four patients with free-end edentulous mandibles. Pressure measurements were obtained by using thin and flexible tactile sensors. The results showed significant variances with different ORDs in all four patients (P < .05), leading to the conclusion that the pressure distribution on the residual ridge beneath the RPD base was dependent on the ORD.

Roles of dentists and dental hygienists in two major earthquakes.

BACKGROUND: In recent years, disasters that overwhelm the capacity of humans have been frequent. However, international cooperation has been swift as a result of advances in transportation, enabling the more prompt administration of First Aid. METHODS: We have had two opportunities to observe outcomes in oral hygiene immediately after and 10 months after two different major disasters. RESULTS: The types of food provided to survivors altered their sense of taste and resulted in the occurrence of dental caries several months after an earthquake. In addition, it is difficult to practise good oral hygiene in the aftermath of a disaster. CONCLUSIONS: We observed the occurrence of previously undocumented problems related to dental issues, such as changes in children's sense of taste caused by unfamiliar types of food provided in relief shelters. Dentists and dental hygienists who are involved in the relief of survivors in the immediate aftermath of a natural disaster should focus on maintaining good oral health in order to prevent the occurrence of dental caries.

Convergent genesis of an adult neural crest-like dermal stem cell from distinct developmental origins.

Skin-derived precursors (SKPs) are multipotent dermal stem cells that reside within a hair follicle niche and that share properties with embryonic neural crest precursors. Here, we have asked whether SKPs and their endogenous dermal precursors originate from the neural crest or whether, like the dermis itself, they originate from multiple developmental origins. To do this, we used two different mouse Cre lines that allow us to perform lineage tracing: Wnt1-cre, which targets cells deriving from the neural crest, and Myf5-cre, which targets cells of a somite origin. By crossing these Cre lines to reporter mice, we show that the endogenous follicle-associated dermal precursors in the face derive from the neural crest, and those in the dorsal trunk derive from the somites, as do the SKPs they generate. Despite these different developmental origins, SKPs from these two locations are functionally similar, even with regard to their ability to differentiate into Schwann cells, a cell type only thought to be generated from the neural crest. Analysis of global gene expression using microarrays confirmed that facial and dorsal SKPs exhibit a very high degree of similarity, and that they are also very similar to SKPs derived from ventral dermis, which has a lateral plate origin. However, these developmentally distinct SKPs also retain differential expression of a small number of genes that reflect their developmental origins. Thus, an adult neural crest-like dermal precursor can be generated from a non-neural crest origin, a finding with broad implications for the many neuroendocrine cells in the body.

TGF-beta mediated FGF10 signaling in cranial neural crest cells controls development of myogenic progenitor cells through tissue-tissue interactions during tongue morphogenesis.

Skeletal muscles are formed from two cell lineages, myogenic and fibroblastic. Mesoderm-derived myogenic progenitors form muscle cells whereas fibroblastic cells give rise to the supportive connective tissue of skeletal muscles, such as the tendons and perimysium. It remains unknown how myogenic and fibroblastic cell-cell interactions affect cell fate determination and the organization of skeletal muscle. In the present study, we investigated the functional significance of cell-cell interactions in regulating skeletal muscle development. Our study shows that cranial neural crest (CNC) cells give rise to the fibroblastic cells of the tongue skeletal muscle in mice. Loss of Tgfbr2 in CNC cells (Wnt1-Cre;Tgfbr2(flox/flox)) results in microglossia with reduced Scleraxis and Fgf10 expression as well as decreased myogenic cell proliferation, reduced cell number and disorganized tongue muscles. Furthermore, TGF-beta2 beads induced the expression of Scleraxis in tongue explant cultures. The addition of FGF10 rescued the muscle cell number in Wnt1-Cre;Tgfbr2(flox/flox) mice. Thus, TGF-beta induced FGF10 signaling has a critical function in regulating tissue-tissue interaction during tongue skeletal muscle development.

Transforming growth factor-beta regulates basal transcriptional regulatory machinery to control cell proliferation and differentiation in cranial neural crest-derived osteoprogenitor cells.

Transforming growth factor-beta (Tgf-beta) signaling is crucial for regulating craniofacial development. Loss of Tgf-beta signaling results in defects in cranial neural crest cells (CNCC), but the mechanism by which Tgf-beta signaling regulates bone formation in CNCC-derived osteogenic cells remains largely unknown. In this study, we discovered that Tgf-beta regulates the basal transcriptional regulatory machinery to control intramembranous bone development. Specifically, basal transcription factor Taf4b is down-regulated in the CNCC-derived intramembranous bone in Tgfbr2(fl/fl);Wnt1-Cre mice. Tgf-beta specifically induces Taf4b expression. Moreover, small interfering RNA knockdown of Taf4b results in decreased cell proliferation and altered osteogenic differentiation in primary mouse embryonic maxillary mesenchymal cells, as seen in Tgfbr2 mutant cells. In addition, we show that Taf1 is decreased at the osteogenic initiation stage in the maxilla of Tgfbr2 mutant mice. Furthermore, small interfering RNA knockdown of Taf4b and Taf1 together in primary mouse embryonic maxillary mesenchymal cells results in up-regulated osteogenic initiator Runx2 expression, with decreased cell proliferation and altered osteogenic differentiation. Our results indicate a critical function of Tgf-beta-mediated basal transcriptional factors in regulating osteogenic cell proliferation and differentiation in CNCC-derived osteoprogenitor cells during intramembranous bone formation.

Epithelial-specific requirement of FGFR2 signaling during tooth and palate development.

Reciprocal interactions between epithelium and mesenchyme are crucial for embryonic development. Fibroblast growth factors (FGFs) are a growth factor family that play an important role in epithelial-mesenchymal tissue interaction. We have generated epithelial-specific conditional knockout mice targeting Fibroblast growth factor receptor 2 (Fgfr2) to investigate the function of FGF signaling during craniofacial development. K14-Cre;Fgfr2(fl/fl) mice have skin defects, retarded tooth formation, and cleft palate. During the formation of the tooth primordium and palatal processes, cell proliferation in the epithelial cells of K14-Cre;Fgfr2(fl/fl) mice is reduced. Thus, FGF signaling via FGFR2 in the epithelium is crucial for cell proliferation activity during tooth and palate development.

TGF-beta mediated Dlx5 signaling plays a crucial role in osteo-chondroprogenitor cell lineage determination during mandible development.

Transforming growth factor-beta (TGF-beta) signaling is crucial for mandible development. During its development, the majority of the mandible is formed through intramembranous ossification whereas the proximal region of the mandible undergoes endochondral ossification. Our previous work has shown that TGF-beta signaling is required for the proliferation of cranial neural crest (CNC)-derived ectomesenchyme in the mandibular primordium where intramembranous ossification takes place. Here we show that conditional inactivation of Tgfbr2 in CNC cells results in accelerated osteoprogenitor differentiation and perturbed chondrogenesis in the proximal region of the mandible. Specifically, the appearance of chondrocytes in Tgfbr2(fl/fl);Wnt1-Cre mice is delayed and they are smaller in size in the condylar process and completely missing in the angular process. TGF-beta signaling controls Sox9 expression in the proximal region, because Sox9 expression is delayed in condylar processes and missing in angular process in Tgfbr2(fl/fl);Wnt1-Cre mice. Moreover, exogenous TGF-beta can induce Sox9 expression in the mandibular arch. In the angular processes of Tgfbr2(fl/fl);Wnt1-Cre mice, osteoblast differentiation is accelerated and Dlx5 expression is elevated. Significantly, deletion of Dlx5 in Tgfbr2(fl/fl);Wnt1-Cre mice results in the rescue of cartilage formation in the angular processes. Finally, TGF-beta signaling-mediated Scleraxis expression is required for tendonogenesis in the developing skeletal muscle. Thus, CNC-derived cells in the proximal region of mandible have a cell intrinsic requirement for TGF-beta signaling.

TGF-beta mediated Msx2 expression controls occipital somites-derived caudal region of skull development.

Craniofacial development involves cranial neural crest (CNC) and mesoderm-derived cells. TGF-beta signaling plays a critical role in instructing CNC cells to form the craniofacial skeleton. However, it is not known how TGF-beta signaling regulates the fate of mesoderm-derived cells during craniofacial development. In this study, we show that occipital somites contribute to the caudal region of mammalian skull development. Conditional inactivation of Tgfbr2 in mesoderm-derived cells results in defects of the supraoccipital bone with meningoencephalocele and discontinuity of the neural arch of the C1 vertebra. At the cellular level, loss of TGF-beta signaling causes decreased chondrocyte proliferation and premature differentiation of cartilage to bone. Expression of Msx2, a critical factor in the formation of the dorsoventral axis, is diminished in the Tgfbr2 mutant. Significantly, overexpression of Msx2 in Myf5-Cre;Tgfbr2flox/flox mice partially rescues supraoccipital bone development. These results suggest that the TGF-beta/Msx2 signaling cascade is critical for development of the caudal region of the skull.

Wnt3a regulates Lef-1 expression during airway submucosal gland morphogenesis.

Regulation of the lymphoid enhancer factor 1 (Lef-1) transcription factor is important for the inductive formation of many epithelial-derived appendages including airway submucosal glands (SMGs). Although Wnts have been linked to developmental processes involving transcriptional activation of the Lef-1 protein, there is little in vivo information directly linking Wnts with the transcriptional regulation of the Lef-1 promoter. In the present study, we hypothesized that Wnt3a directly regulates Lef-1 gene expression required for SMG morphogenesis in mice. In support of this hypothesis, TOPGAL reporter mice demonstrated activation of beta-catenin/Tcf complexes during early phases of SMG development and immunolocalization studies confirmed abundant expression of Tcf4, but not Tcf1 or Tcf3, at this stage. ChIP analysis in primary airway epithelial cells revealed that Tcf4 associates with a known Wnt Responsive Region in the Lef-1 promoter and transfection of Cos-1 cells with dominant active beta-catenin and Tcf4 synergistically activated the Lef-1 promoter. Using Wnt3a deficient and Lef-1 promoter-GFP reporter mice, we also demonstrate that Wnt3a induces Lef-1 gene expression in newly forming SMG buds of mice and is required for the maintenance of gland bud growth. These findings provide the first in vivo evidence that Wnt3a can transcriptionally regulate the Lef-1 gene.

TGF-beta signaling and aplasia cutis congenita: proposed animal model.

TGF-beta plays a role in cell migration, proliferation, and differentiation during embryonic development. This study investigated the effect of neural crest- or mesodermspecific loss of TGF-beta type II receptor in mice. These conditional knockout mice both exhibit skin defects of the skull associated with an underlying bone defect, a phenotype consistent with the human disorder aplasia cutis congenita. The authors suggest that TGF-3 type II receptor gene is a candidate gene for aplasia cutis congenita.

Functional significance of Smad2 in regulating basal keratinocyte migration during wound healing.

Members of the transforming growth factor-beta (TGF-beta) superfamily are critical regulators for wound healing. Transduction of TGF-beta signaling depends on activation of Smad2 and Smad3 by heteromeric complexes of ligand-specific receptors. Mice lacking Smad3 show accelerated wound healing, whereas the biological significance of Smad2-mediated TGF-beta signaling in wound healing remains unknown. To understand the function of Smad2 in regulating wound healing, we investigated the effect of Smad2 overexpression on epithelialization of incision wounds. Cutaneous wounds made in K14-Smad2 mice showed delayed healing. This delay in wound healing resulted from a defect in basal keratinocyte migration in K14-Smad2 mice. Instead of basal keratinocytes, the suprabasal layer of keratinocytes migrated into the wound region. Furthermore, overexpression of Smad2 activated the Smad2/Smad4 complex in keratinocytes and inhibited keratin 16 (K16) expression. As K16 functions as a critical mediator for reorganization of keratin filaments following skin injury, we propose that altered K16 expression affects the migration of basal keratinocytes in the K14-Smad2 mice. Taken together, these findings demonstrate a crucial role of TGF-beta signaling mediator Smad2 in regulating keratinocyte migration and re-epithelialization during wound healing. The K14-Smad2 transgenic mice can serve as an animal model for the investigation of TGF-beta signaling mechanism in regulating wound healing.

A signaling pathway involving TGF-beta2 and snail in hair follicle morphogenesis.

In a common theme of organogenesis, certain cells within a multipotent epithelial sheet exchange signals with their neighbors and develop into a bud structure. Using hair bud morphogenesis as a paradigm, we employed mutant mouse models and cultured keratinocytes to dissect the contributions of multiple extracellular cues in orchestrating adhesion dynamics and proliferation to shape the cluster of cells involved. We found that transforming growth factor beta2 signaling is necessary to transiently induce the transcription factor Snail and activate the Ras-mitogen-activated protein kinase (MAPK) pathway in the bud. In the epidermis, Snail misexpression leads to hyperproliferation and a reduction in intercellular adhesion. When E-cadherin is transcriptionally down-regulated, associated adhesion proteins with dual functions in signaling are released from cell-cell contacts, a process which we demonstrate leads to Ras-MAPK activation. These studies provide insights into how multipotent cells within a sheet are stimulated to undergo transcriptional changes that result in proliferation, junctional remodeling, and bud formation. This novel signaling pathway further weaves together the web of different morphogens and downstream transcriptional events that guide hair bud formation within the developing skin.