Effect of local bone marrow stromal cell administration on ligature-induced periodontitis in mice.

Bone marrow-derived multipotent stromal cells (BMSCs) have potent antiinflammatory effects. This study aimed to investigate the antiinflammatory potential of BMSCs using a mouse model of ligature-induced periodontitis. BMSCs were isolated from the femurs and tibiae of mice. Periodontitis was induced by placing a ligature around the right maxillary second molar. After 3 days, the mice were administered BMSC in the gingiva of the mesial interdental papilla around the ligatured molar. The ligatured and non-ligatured mice that were not administered BMSC served as controls. Differences in inflammatory infiltration and bone resorption around the roots of the second molar were assessed and were subsequently quantified using microcomputed tomography (micro-CT), histological analysis, and tartrate-resistant acid phosphatase (TRAP) staining. Micro-CT revealed that alveolar bone loss around the ligatured molars increased in a time-dependent manner; however, the effect was significantly less in BMSC-treated mice compared with ligatured control mice. Tissue histopathology revealed that BMSC administration mitigated inflammatory infiltration in ligatured BMSC mice. In addition, the number of TRAP-positive osteoclasts was markedly elevated in ligatured control mice compared with those in BMSC-treated mice. These findings indicate that local BMSC administration can mitigate inflammation and alveolar bone resorption, suggesting that administering BMSC leads to new therapeutics for periodontitis.

Transplantation of mature adipocyte-derived dedifferentiated fat cells into three-wall defects in the rat periodontium induces tissue regeneration.

The transplantation of dedifferentiated fat (DFAT) cells in combination with poly(d,l-lactic-co-glycolic acid) (PLGA) scaffolds has previously been proven as an effective approach in promoting periodontal tissue regeneration in a rat fenestration defect model. The aim of this study was to assess the regenerative potential of DFAT cells in a rat model of three-wall periodontal bone defect. Three-wall bone defects were created bilaterally on the mesial side of rat maxillary first molars and were either left untreated or treated by implantation of PLGA scaffolds with DFAT cells or PLGA alone. Four weeks after surgery, the tissues were processed for micro-computed tomography (micro-CT) and histomorphometric examination. Micro-CT revealed that the PLGA/DFAT group had significantly higher rates of bone regeneration than the other groups, while histomorphometric analysis showed that the PLGA/DFAT group had significantly higher densities of collagen fiber bundles in acellular and cellular cementum than the PLGA group. Moreover, the results indicate that the placement of the PLGA scaffold prevented the downgrowth of the junctional epithelium. These findings suggest that DFAT cells contribute to tissue regeneration in three-wall periodontal defects, while PLGA provides space necessary for periodontal tissue restoration.

Induction of neural crest cells from human dental pulp-derived induced pluripotent stem cells.

We previously generated induced pluripotent stem (iPS) cells from human dental pulp cells of deciduous teeth. Neural crest cells (NCCs) play a vital role in the development of the oral and maxillofacial region. Therefore, NCCs represent a cell source for bone, cartilage, and tooth-related tissue engineering. In this study, we examined whether iPS cells are capable of differentiating into NCCs through modification of the human embryonic stem cell protocol. First, iPS cells were dissociated into single cells and then reaggregated in low-cell-adhesion plates with neural induction medium for 8 days in suspension culture to form neurospheres. The neurospheres were transferred to fibronectin-coated dishes and formed rosette structures. The migrated cells from the rosettes abundantly expressed NCC markers, as evidenced by real-time polymerase chain reaction, immunofluorescence, and flow cytometric analysis. Furthermore, the migrated cells exhibited the ability to differentiate into neural crest lineage cells in vitro. They also exhibited tissue-forming potential in vivo, differentiating into bone and cartilage. Collectively, the migrated cells had similar characteristics to those of NCCs. These results suggest that human dental pulp cell-derived iPS cells are capable of differentiating into NCCs. Therefore, iPS cell-derived NCCs represent cell sources for bone and cartilage tissue engineering.

Systematic review and assessment of systematic reviews examining the effect of periodontal treatment on glycemic control in patients with diabetes

OBJECTIVES: There have been several systematic reviews(SRs) on whether periodontal treatment for an individual with both periodontal disease and diabetes can improve diabetes outcomes. The purpose of this investigation was to conduct a systematic review (SR) of previous meta-analyses, and to assess the methodological quality of the SRs examining the effects of periodontal treatment and diabetes. (PROSPERO Registration # CRD 42015023470). Study DESIGN: We searched five electronic databases and identified previous meta-analyses of randomized controlled trials published through July 2015. In cases where the meta-analysis did not meet our criteria, the meta-analyses were recalculated. General characteristics of each included trial were abstracted, analyzed, and compared. The mean difference, 95% confidence intervals (CIs) and the I2 statistic were abstracted or recalculated. The Assessment of Multiple Systematic Reviews Instrument (AMSTAR) was used to assess methodological quality. RESULTS: Of the 475 citations screened, nine systematic reviews were included. In total, 13 meta-analyses included in nine SRs were examined. In comparability analyses, meta-analyses in four SRs did not meet our criteria, and were recalculated. Of these 13 meta-analyses, 10 suggested significant effects of periodontal treatment on HbA1c improvement. Mean differences found in the 13 meta-analyses ranged from -0.93 to 0.13. AMSTAR assessment revealed six SRs with moderate and three with high overall quality. CONCLUSIONS: We can conclude that there is a significant effect of periodontal treatment on improvement of HbA1c in diabetes patients, although the effect size is extremely small. In addition to the small effect size, not all SRs could be considered of high quality

Multimodal Chemosensory Circuits Controlling Male Courtship in Drosophila.

Throughout the animal kingdom, internal states generate long-lasting and self-perpetuating chains of behavior. In Drosophila, males instinctively pursue females with a lengthy and elaborate courtship ritual triggered by activation of sexually dimorphic P1 interneurons. Gustatory pheromones are thought to activate P1 neurons but the circuit mechanisms that dictate their sensory responses to gate entry into courtship remain unknown. Here, we use circuit mapping and in vivo functional imaging techniques to trace gustatory and olfactory pheromone circuits to their point of convergence onto P1 neurons and reveal how their combined input underlies selective tuning to appropriate sexual partners. We identify inhibition, even in response to courtship-promoting pheromones, as a key circuit element that tunes and tempers P1 neuron activity. Our results suggest a circuit mechanism in which balanced excitation and inhibition underlie discrimination of prospective mates and stringently regulate the transition to courtship in Drosophila.

Bone regeneration with systemic administration of lactoferrin in non-critical-sized rat calvarial bone defects.

Using in vivo microfocus computed tomography (micro-CT) and tissue sections, we evaluated bone regeneration in non-critical-sized rat calvarial flat bone defects during systemic administration of lactoferrin (LF). Ten 11-week-old male Fischer rats were used. Non-critical-sized calvarial bone defects (diameter, 2.7 mm) were trephined into the dorsal parietal bone on both sides of the midsagittal suture, and a collagen sponge soaked in saline was placed on each side. LF was injected intraperitoneally every day, starting on the day of the operation (day 0; groups: control, 10 mg/kg LF, 100 mg/kg LF). Micro-CT imaging was performed repeatedly from 1 to 4 weeks after surgery. The defect sites were then removed, along with surrounding bone and soft tissues, and stained with hematoxylin and eosin. During weeks 1-4, micro-CT showed a significant difference in reossification ratio between the controls and the 100 mg/kg LF group. Histological analysis revealed that there were more osteoblast-like cells around the bony rim in the 100 mg/kg group than in the control group. In summary, micro-CT and histological analyses showed that systemic administration of LF accelerated bone regeneration in non-critical-sized rat calvarial bone defects.

A single pair of interneurons commands the Drosophila feeding motor program.

Many feeding behaviours are the result of stereotyped, organized sequences of motor patterns. These patterns have been the subject of neuroethological studies, such as electrophysiological characterization of neurons governing prey capture in toads. However, technical limitations have prevented detailed study of the functional role of these neurons, a common problem for vertebrate organisms. Complexities involved in studies of whole-animal behaviour can be resolved in Drosophila, in which remote activation of brain cells by genetic means enables us to examine the nervous system in freely moving animals to identify neurons that govern a specific behaviour, and then to repeatedly target and manipulate these neurons to characterize their function. Here we show neurons that generate the feeding motor program in Drosophila. We carried out an unbiased screen using remote neuronal activation and identified a critical pair of brain cells that induces the entire feeding sequence when activated. These 'feeding neurons' (here abbreviated to Fdg neurons for brevity) are also essential for normal feeding as their suppression or ablation eliminates sugar-induced feeding behaviour. Activation of a single Fdg neuron induces asymmetric feeding behaviour and ablation of a single Fdg neuron distorts the sugar-induced feeding behaviour to become asymmetric, indicating the direct role of these neurons in shaping motor-program execution. Furthermore, recording neuronal activity and calcium imaging simultaneously during feeding behaviour reveals that the Fdg neurons respond to food presentation, but only in starved flies. Our results demonstrate that Fdg neurons operate firmly within the sensorimotor watershed, downstream of sensory and metabolic cues and at the top of the feeding motor hierarchy, to execute the decision to feed.