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1.
2.

Objective

A RANKL-binding peptide, WP9QY (W9), is known to inhibit mouse osteoclastogenesis by stimulating the production of autocrine factors such as bone morphogenetic proteins (BMPs) to induce osteoblast differentiation. In the present study, we investigated whether osteoblastic differentiation is mediated by RANKL signaling.

Methods

The effect of W9 on the differentiation of osteoclasts and osteoblasts was examined in mouse bone-marrow cultures, and in a mouse co-culture system consisting of primary osteoblasts derived from RANKL-deficient or wild-type (WT) newborn mouse calvariae, with WT-derived bone marrow mononuclear cells.

Results

The addition of the W9 peptide to the WT mouse bone-marrow culture simultaneously inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation, and stimulated alkaline phosphatase (ALP)-positive osteoblastic calcified nodule formation. RANKL-deficient osteoblasts exhibited weak ALP activity compared to WT osteoblasts. W9 treatment strongly inhibited TRAP-positive osteoclast formation, and stimulated ALP-positive osteoblast differentiation in co-cultures of WT-derived osteoblasts and bone-marrow cells, in the presence of bone-resorbing factors. In contrast, W9 exerted only a weak effect on ALP-positive osteoblast differentiation in co-cultures with RANKL-deficient osteoblasts, even in the presence of the W9 peptide, parathyroid hormone, and/or BMP-2.

Conclusions

The W9 peptide inhibited RANKL-mediated osteoclast formation in osteoblasts. It also directly stimulated osteoblast differentiation, both via RANKL signaling-mediated autocrine factors, and alternative mechanisms.  相似文献   

3.

Background

The Golgi apparatus is at a crossroads between anterograde and retrograde trafficking. It exhibits a twisted ribbon-like network in the juxtanuclear region of vertebrate cells. Vesicle-associated membrane protein 4 (VAMP4) is a unique v-SNARE expressed exclusively in trans-Golgi networks (TGN), where it regulates retrograde trafficking from the early endosome to the TGN with its cognate SNARE partners Syntaxin 6, Syntaxin 16, and Vti1a.

Highlight

To examine whether VAMP4 plays a role in maintaining the Golgi ribbon structure, we depleted VAMP4 expression using a small interfering RNA. Depletion of VAMP4 led to fragmentation of the Golgi ribbon in HeLa cells. Immunohistochemical analysis showed that, in the absence of VAMP4, although the Golgi stack length was shortened, Golgi stacking was normal. Furthermore, depletion of the cognate SNARE partners of VAMP4 also disrupted the Golgi ribbon structure. Microscopy-based analyses showed that Golgi fragmentation did not impair anterograde traffic.

Conclusion

Our findings suggest that VAMP4 and its cognate SNAREs are required for maintaining the Golgi ribbon structure by balancing membrane transport between the endosome and TGN.  相似文献   

4.

Background

Dentin hypersensitivity is a relatively common pain symptom caused by evaporative, chemical, thermal, tactile, or osmotic stimuli. Despite its high prevalence, many aspects of dentin hypersensitivity remain unknown. Current treatments for dentin hypersensitivity include desensitizers and adhesive materials. Several factors that occur in the oral cavity, such as occlusal force and intrapulpal pressure, cause microleakage, the primary defect of adhesive treatments.

Highlight

(1) This review article explains the etiology and pain mechanisms of dentin hypersensitivity. (2) Microleakage, a primary cause of restoration failures, is emphasized. (3) Current and ideal treatments for dentin hypersensitivity are described.

Conclusion

The ideal treatment for dentin hypersensitivity should restore the original impermeability of the dentinal tubules. A novel way to treat dentin hypersensitivity is the regeneration of tubular dentin to overcome microleakage.  相似文献   

5.

Background

Porphyromonas gingivalis is s major oral bacterium closely associated with periodontal diseases including periodontitis and directly affects host cellular signaling. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays multiple roles in various cell functions including cell survival and glucose metabolism. In this review, we describe the effect of gingipains on the PI3K/Akt signaling pathway in P. gingivalis infection.

Highlight

Gingipains inactivate PI3K and Akt in gingival epithelial cells infected with P. gingivalis. These events occur independently of invasion of this organism into the cells and are required for the enzymatic activity of gingipains. Furthermore, 3-Phosphoinositide-dependent protein kinase-1 (PDK1) failed to translocate to the plasma membrane from the cytosol following PI3K inactivation.Additionally, dephosphorylation of Akt downstream proteins, including glycogen synthase kinase 3 (GSK3), mammalian target of rapamycin (mTOR), and Bad, occurs in parallel with the dysregulation of PI3K/PDK1/Akt cascades.

Conclusion

This review describes the biological characterization of gingipains, which inactivate PI3K and Akt, and disorder the PI3K/Akt signaling pathway. Hence, gingipains may decrease cellular physiological functions, eventually disrupting the gingival epithelium and causing development of periodontal diseases.  相似文献   

6.
7.

Background

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic ossification (HO) in soft tissues such as skeletal muscles, tendons, and ligaments. Gain-of-function mutations in ALK2, a type I receptor for bone morphogenetic proteins (BMPs), have been identified in patients with FOP; however, the molecular mechanisms that result in the activation of ALK2 mutants remain unclear.

Highlight

FOP-associated mutant ALK2 signaling is further enhanced by BMP type II receptor in a serine/threonine kinase activity-dependent manner. The threonine residue at position 203 (T203) in ALK2 is crucial for this enhancement by BMP type II receptor. Recently, activin A was found to be a critical ligand of ALK2 mutants.

Conclusion

BMP type II receptor-dependent phosphorylation of ALK2 mutants in response to ligand binding is important for the activation of BMP signaling in FOP. Therefore, the use of anti-activin A compounds would be a novel treatment approach for FOP.  相似文献   

8.

Objectives

We have previously demonstrated that phospholipase C-related catalytically inactive protein (PRIP) is involved in fat metabolism and energy consumption. However, whether PRIP participates in body energy metabolism in vivo remains to be determined. Therefore, we examined whether PRIP deficiency affects whole-body energy homeostasis, which is modulated by non-shivering thermogenesis in brown adipose tissue, using a cold exposure animal model.

Methods

Fasting plasma triacylglycerol levels were measured to evaluate fat metabolism in wild-type and Prip-KO mice. In addition, a glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. To determine changes in energy consumption, mice were exposed to a cold environment for 7 days, and expression of uncoupling protein 1 (UCP1) in brown adipose tissue was analyzed via western blotting.

Results

Fasting plasma levels of triacylglycerols were significantly higher in Prip-KO mice than in wild-type mice. However, Prip-KO mice showed a healthy phenotype based on GTT and ITT. UCP1 expression was significantly upregulated in the brown and white adipose tissues of Prip-KO mice exposed to cold conditions.

Conclusion

Prip-KO mice exhibit greater ability to consume lipids as an energy source, indicating that PRIP modulates of systemic energy expenditure. Our findings provide increased understanding of PRIP-mediated non-shivering thermogenic mechanisms and offers important insights for the treatment and control of obesity.  相似文献   

9.

Objectives

The relationship between length of leisure time and periodontal condition is unknown. The aim of this cross-sectional study was to clarify the association between leisure time and periodontal states.

Methods

This study was conducted on a cross-sectional sample of male (n=68) and female (n=30) Japanese healthy workers aged between 22 and 75 years. Periodontal states, including probing pocket depth, attachment level, bleeding on probing and serum antibody level for periodontal bacteria, and self-reported work conditions were assessed.

Results

Subjects with long leisure times on a weekday showed increased probing pocket depth and attachment loss compared to subjects with shorter free times. The serum antibody level of a major periodontal pathogen, Porphyromonas gingivalis, was higher in the long leisure group than in the short time group.

Conclusions

Subjects with long leisure time showed aggregated periodontal condition consistent with increased serum antibody against periodontal bacteria compared to subjects with short free time.  相似文献   

10.

Objective

Sp7 is required for cellular cementum formation and odontoblast differentiation in the root. Sp7 is expressed in preodontoblasts and is strongly expressed in odontoblasts. However, Sp7 expression was down-regulated in odontoblasts in the crown after root formation. We examined osteoblast/odontoblast-specific Sp7 transgenic mice to investigate the effects of sustained Sp7 expression in differentiated odontoblasts.

Methods

Tooth development was examined by immunohistochemical analyses, using antibodies against Sp7, pro-collagen type1a1, osteocalcin, dentin sialoprotein (DSP), nestin, and osteopontin.

Results

In 1-week-old Sp7 transgenic mice, the thickness of dentin was slightly reduced, the elongation of odontoblasts was inhibited, and odontoblasts in the cusp lost polarity. At 2 weeks of age, Sp7 was strongly expressed in odontoblasts in the root, but weakly expressed in the crown of wild-type mice. It was strongly expressed in odontoblasts in the crown and root and the thinning of dentin and impairments in elongation and polarization in odontoblasts were severe in the crown of Sp7 transgenic mice. Tooth fracture and pulp exposure occurred after tooth eruption. Expression of dentin matrix proteins (DSP and osteocalcin) and nestin were reduced, whereas the osteoblast marker gene, osteopontin, was not expressed in the odontoblasts of Sp7 transgenic mice.

Conclusions

These results indicate that sustained Sp7 expression in differentiated odontoblasts inhibits odontoblast maturation and reduces the expression of dentin matrix proteins; however, it fails to induce the transdifferentiation of odontoblasts into osteoblasts, which occurs in Runx2 transgenic mice. Therefore, Sp7 expression needs to be down-regulated to an appropriate level for odontoblast maturation.  相似文献   

11.

Background

3,3’-diaminobenzidine tetrazolium (DAB)-based methods have been developed to detect the localization of peroxidase (PO) activity. Histochemically, endogenous PO activity has been localized to acini of human and rodent salivary glands. This suggests that the enzyme may be used as a convenient marker of differentiated acinar cells to study factors that influence the development of the rat submandibular gland. We also investigated endogenous PO localization differences between rodent and insectivora (Suncus murinus) major salivary glands by light and electron microscopy. Moreover, ectopic sublingual gland-like tissue was found in the resin-embedded semi-thin sections of DAB-reacted hamster submandibular gland by confocal laser scanning microscopy.

Highlight

Reflectance-mode confocal laser scanning microscopy was employed to visualize sites of PO activity in ectopic sublingual gland-like tissue of the hamster submandibular gland.

Conclusion

The technique proposed here may result in novel applications for DAB-based histochemistry.  相似文献   

12.

Background

Gymnemic acids, triterpene glycosides, are known to act as human-specific sweet inhibitors. The long-lasting effect of gymnemic acids is diminished by γ-cyclodextrin. Here, we focus on the molecular mechanisms underlying the interaction between gymnemic acids and sweet taste receptor and/or γ-cyclodextrin by a sweet taste receptor assay in transiently transfected HEK293 cells.

Highlight

Application of gymnemic acids inhibited intracellular calcium responses to sweet compounds in HEK293 cells expressing human TAS1R2+TAS1R3 but not in those expressing the mouse sweet receptor Tas1r2+Tas1r3 after application of gymnemic acids. The effect of gymnemic acids was reduced after rinsing cells with γ-cyclodextrin. Based on species-specific sensitivities to gymnemic acids, we showed that the transmembrane domain of hTAS1R3 is involved in the sensitivity to gymnemic acids. Point mutation analysis in the transmembrane domain of hTAS1R3 revealed that gymnemic acids shared the same binding pocket with another sweet inhibitor, lactisole. Sensitivity to sweet compounds was also reduced by mixtures of glucuronic acid, a common gymnemic acid. In our molecular models, gymnemic acids interacted with a binding site formed in the transmembrane domain of hTAS1R3.

Conclusion

Gymnemic acids inhibit sweet responses in humans through an interaction between the glucuronosyl group of gymnemic acids and the transmembrane domain of hTAS1R3. Our molecular model provides a foundation for the development of taste modifiers.  相似文献   

13.
14.

Objective

It has previously been shown that oral immunization with the 40-kDa outer membrane protein of Porphyromonas gingivalis (40k-OMP) and CpG oligodeoxynucleotides (ODN) as an adjuvant elicits protective antibody responses against alveolar bone loss caused by P. gingivalis infection. The objective of the present work was to assess the efficacy of this same oral vaccine on prevention of P. gingivalis-accelerated atherosclerosis.

Methods

Apolipoprotein E-deficient spontaneously hyperlipidemic (Apoeshl) mice were orally immunized with 40k-OMP plus CpG ODN and subsequently challenged intravenously with P. gingivalis. The mice were euthanized 15 weeks later, and atheromatous lesions in the proximal aorta of each mouse were analyzed histomorphometrically. Serum concentrations of 40k-OMP-specific antibodies and cytokines as well as levels of proatherogenic factors in the aorta were determined.

Results

P. gingivalis challenge resulted in an increase in the areas of the aortic sinus covered with atherosclerotic plaque, as well as in the levels of high-sensitive C-reactive protein (hsCRP) and some cytokines and chemokines, when compared with sham-treated mice. In contrast, oral immunization with 40k-OMP plus CpG ODN induced 40k-OMP-specific serum IgG responses, and significantly reduced atherosclerotic plaque accumulation in the aortic sinus, along with hsCRP and the cytokine and chemokine levels.

Conclusions

These results suggest that oral administration of 40k-OMP plus CpG ODN may be an effective vaccine for the prevention of accelerated atherosclerosis caused by P. gingivalis infection.  相似文献   

15.

Objectives

The mechanisms regulating positional and ultrastructural changes in peripheral pulp capillaries during dentinogenesis have yet to be fully elucidated. This study aimed to clarify the relationship between the spatiotemporal localization and ultrastructure of peripheral capillaries and the dentin deposition and mineralization rate.

Methods

Maxillary first molars of 5- to 100-day-old Wistar rats were collected and prepared for transmission electron microscopy. The animals who had received multiple injections of lead disodium ethylenediaminetetraacetic acid were analyzed for dentin deposition rate. Non-demineralized maxillae were examined with an electron probe micro analyzer.

Results

The dentin deposition rate at the coronal position where dentinogenesis began on day 5 reached a peak during days 10–30, gradually decreased, and ceased on day 60. The mineral content of enamel was low on day 10 (the secretory stage of amelogenesis), drastically increased on day 15 (the maturation stage of amelogenesis), and reached a maximum and persisted until day 30. The dentin underneath the maturing enamel exhibited a synchronous increase in mineral content. The distance between the mineralization front and peripheral capillaries remained almost constant, suggesting that the positional changes of capillaries into the odontoblast layer were not due to migration of capillaries but could be attributed to an increase in the height of the odontoblast layer. Endothelial fenestrations became prominent in the most active phase of dentin deposition and mineralization.

Conclusions

These results indicate that the positional and ultrastructural changes in peripheral capillaries correlate with the active phase of dentin deposition and mineralization.  相似文献   

16.

Background

Bones adapt to loads by changing their structure. This biomechanical interaction and the formation/maintenance of bones are orchestrated by three major cell types residing in the bones: osteoblasts, osteocytes, and osteoclasts. Recent findings suggest that, in addition to their biomechanical interactions, bones and other organ systems may also communicate biochemically.

Highlight

This brief review will discuss the interaction between the bones and the nervous system, vasculature, muscle, and fat tissues, with an emphasis on the role of the energy metabolism in these interactions.

Conclusion

Studies on the connections between bones and other organ systems indicate the possible existence of a temporospatial pattern of energy metabolism through the cellular biorhythm and migration.  相似文献   

17.

Background

The oral cavity is a propitious environment for bacteria with different tissue tropisms to colonize and grow due to its diverse surfaces. For bacterial survival in the oral cavity, where tissues are continuously bathed in fluids, biofilm formation is necessary. Dental biofilm, i.e. dental plaque, is notoriously hard to inhibit and traditional oral care solutions are either ineffective at managing oral biofilms or cause secondary effects, such as teeth staining, that make them unattractive.

Highlight

Chitosan has high biocompatibility and antimicrobial activity that is heralded by the pharmaceutical industry for its applicability in biofabrication. Therefore, this material is a potential substitute for the antimicrobials traditionally used in oral care.

Conclusion

Currently, the body of work on chitosan and the oral cavity ranges from planktonic studies in vitro to biofilm control/removal studies in vivo. With a wide range of topics available for analysis, this review provides a working understanding of chitosan's role in the control and management of oral biofilms.  相似文献   

18.

Background

Since salivary fluid is created from blood plasma, hemodynamics in the salivary glands play an important role in the production of saliva. Trigeminal sensory input induces both salivary secretion and reflex parasympathetic vasodilation in salivary glands. This glandular vasodilation is thought to be important for the regulation of glandular hemodynamics due to the rapidity with which blood flow is increased. This review article summarizes recent research on the involvement of parasympathetic vasodilation in regulating hemodynamics in the salivary gland.

Highlight

Electrical stimulation of the lingual nerve, a branch of the trigeminal nerve, elicits parasympathetic vasodilation in the salivary glands. Parasympathetic vasodilation is mainly evoked by cholinergic fibers in the submandibular and parotid glands and by cholinergic and vasoactive intestinal peptide (VIP)-ergic fibers in the sublingual gland. The vasodilator mechanism changes from cholinergic to VIP-ergic when muscarinic receptors are deactivated.

Conclusion

Glandular hemodynamics in the submandibular, parotid, and sublingual glands are regulated by different parasympathetic vasodilator mechanisms, which may functionally contribute to the differences in secretion among the major salivary glands.  相似文献   

19.

Background

Bone strength, which is an indicator of the risk of fracture, is determined by bone mass (bone mineral density, 70%) and bone quality (30%). Bone quality results from a combination of various material and structural properties, making it difficult to determine a suitable method for the evaluation of bone quality based on clinical measurements. Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy are powerful techniques for the assessment of bone quality and reveal similar information on molecular structures; however, this molecular information is based on different physical phenomena. Therefore, a comparison of FTIR and Raman spectra is required for an accurate assessment of bone quality.

Highlight

We previously assessed the bone quality of femurs from rats with chronic kidney disease (CKD) using FTIR imaging, and found the carbonate-to-phosphate ratio in the hydroxyapatite was significantly reduced compared to control rats; however, there was no difference in crystallinity. Therefore, we focused on the crystallinity of the femoral cortical bone in rats with CKD, and compared the PO43- bands in FTIR spectra in detail with those in the Raman spectra.

Conclusion

The PO43- bands in the FTIR spectra were affected by changes in calcium phosphate composition rather than by changes in crystal size. Thus, FTIR is more suitable for the evaluation of mineral maturity than crystallinity; Raman spectroscopy is more sensitive to crystallinity than FTIR.  相似文献   

20.

Objectives

We previously reported that masseter motoneurons (MMNs) and digastric motoneurons (DMNs) in postnatal day (P) 1–5 rats receive convergent inputs from the lateral (l-) and medial (m-) supratrigeminal regions (SupV), intertrigeminal region (IntV), and dorsal region of the principal sensory trigeminal nucleus (PrV). The l-SupV sends burst inputs predominantly to the MMNs. We compared the synaptic inputs to P9–12 rat MMNs and DMNs with those found in the previous study involving P1–5 rats.

Methods

We performed whole-cell recordings and laser photolysis of caged glutamate in the MMNs and DMNs of P9–12 rats.

Results

Similar to P1–5 rats, the photostimulation of multiple regions within the l-SupV, m-SupV, IntV, and dorsal PrV, induced postsynaptic currents (PSCs) in both P9–12 MMNs and DMNs. Photostimulation induced predominantly low-frequency PSCs in both P9–12 motoneurons, whereas l-SupV photostimulation predominantly induced burst PSCs in P1–5 rats. However, when the caged glutamate concentration was doubled, l-SupV photostimulation evoked burst PSCs in all P9–12 MMNs. Furthermore, l-SupV and m-SupV photostimulation evoked burst or low-frequency PSCs at significantly higher rates in the MMNs compared to in the DMNs.

Conclusions

These results suggested that, similar to P1–5 motoneurons, both P9–12 motoneurons received convergent inputs from the SupV, IntV, and PrV; however, the input–output gains of some of the premotor neurons decreased. These synaptic input changes may contribute to the proper development of chewing.  相似文献   

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