Regulatory mechanisms of periodontal regeneration

The periodontal ligament, located between the cementum and the alveolar bone, has a width ranging from 0.15 to 0.38 mm. Regeneration and homeostasis of the periodontal ligament are highly significant functions in relation to periodontal therapy, tooth transplantation or replantation, and orthodontic tooth movement. The purpose of this review is to discuss the regulatory mechanisms of regenerative and homeostatic functions in the periodontal ligament based on currently published studies and also on our own experimental data. We consider the capability of the ligament tissue to promote or to suppress calcification in connection with bone and cementum formation and the maintenance of the periodontal ligament space. Also discussed are the involvement of the periodontal ligament tissue in the regenerative ability, cell proliferation, growth and differentiation factors, extracellular matrix proteins, homeostatic phenomena, function of Malassez epithelial rests, tooth movement, or occlusal loading. Regulatory mechanisms for regeneration and homeostasis of the periodontal ligament are hypothetically proposed.     

Periodontal research contributions to basic sciences: From cell communication and host-parasite interactions to inflammation and bone biology

The periodontium comprises all structures surrounding the teeth, including gingiva, root cementum, periodontal ligament and alveolar bone. Those tissues aim to protect and support the teeth and are challenged by a residing microbiota that leads to subclinical inflammation even in physiological conditions. Periodontitis, a prevalent multicausal inflammatory and destructive disease, develops as a result from complex host-parasite interactions. This unique physiologic and pathologic scenario enables the development of research methods which allows conclusions beyond the simple understanding of periodontal homeostasis. The aim of this viewpoint was to explore potential contributions of periodontal research to a wide array of basic science specialties, such as cell and molecular biology, microbiology, immunology, endocrinology, rheumatology, among others.     

Age-dependent changes of the periodontal ligament in rats

Even after the end of the natural tooth eruption, there is a continuous renewal of the periodontal collagenous fiber system, depending on functional demands. The aim of this study was to analyse the age-dependent changes and regional differences of the collagen renewal rate of the periodontal ligament in healthy rats. The study was performed by autoradiography of the molars of rats aged 1, 8, and 18 months, where collagen was labelled by intravenously applied 3H-proline. After an 8-hour incorporation period, the animals were killed. For comparative examinations, molar roots were subdivided into cervical, middle, and apical thirds. Structural and quantitative analyses were performed by light microscopy and autoradiography, using an image-analysing computer-assisted operating unit that determined the 3H-proline-labelled collagen by photometry based on extinction measurement. With increasing age of the animals, the number of silver grains (3H-proline-blackened collagen) was reduced and the quantitative evaluation indicated a reduction of 3H-proline in the periodontal ligament. The lowest level of 3H-proline activities was observed in the middle, and the highest level in the apical root third, independent of age. All preparations revealed condensations of silver grains, which were located in the region of the periodontal ligament adjacent to the alveolar bone, but did not reveal any preferred position with regard to the dental topography. With progressive age, the uptake of 3H-proline in the periodontal ligament was reduced by about 20 to 30%, a result that corresponds to a decrease in collagenous fiber production. Collagen was mainly formed in the apical and cervical root third, starting from the alveolar bone side, presumably in response to functional strain.     

Regeneration of periodontal Ruffini endings in adults and neonates

We reviewed the regeneration of periodontal Ruffini endings, primary mechanoreceptors in the periodontal ligament, following injury to the inferior alveolar nerve (IAN) in adult and neonatal rats. Morphologically, mature Ruffini endings are characterized by an extensive arborization of axonal terminals and association with specialized Schwann cells, called lamellar or terminal Schwann cells. Following injury to IAN in the adult, the periodontal Ruffini endings of the rat lower incisor ligament regenerate more rapidly than Ruffini endings in other tissues. During regeneration, terminal Schwann cells migrate into regions where they are never found under normal conditions. The development of periodontal Ruffini endings of the rat incisor is closely associated with the eruption of the teeth; the morphology and distribution of the terminal Schwann cells became almost identical to those in adults during postnatal days 15-18 (PN 15-18d) when the first molars appear in the oral cavity, while the axonal elements showed extensive ramification around PN 28d when the functional occlusion commences. When the IAN was injured in neonates, the regeneration of periodontal Ruffini endings was delayed compared with the adults. The migration of terminal Schwann cells is also observed following IAN injury, after which the distribution of terminal Schwann cells became almost identical to that of the adults, i.e., PN 14d. Since the interaction between axon and Schwann cell is important during regeneration and development, further studies are required to elucidate its molecular mechanism during the regeneration as well as the development of the periodontal Ruffini endings.     

Resin luting materials: Tissue response in dog's teeth

The aim of this study was to evaluate radiographically and histologically the pulpal and periapical response to self‐adhesive (Rely X? Unicem) and self‐etching and self‐curing (Multilink^®) resin‐based luting materials in deep cavities in dogs' teeth. Deep class V cavities (0.5‐mm–thick dentin) were prepared in 60 canine premolars and the following materials were applied on cavity floor: Groups I/V—RelyX? Unicem; Groups II/VI—Multilink^®; Groups III/VII—zinc phosphate cement (control) and; Groups IV/VIII—gutta‐percha (control). Cavities were restored with silver amalgam. Animals were euthanized after 10 days (groups I–IV) and 90 days (groups V–VIII). Tooth/bone blocks were radiographed and processed for histopathological evaluation of pulp and periapical tissue response to the materials. All materials presented similar histopathological features and radiographic findings at both periods. The pulp tissue was intact. The apical and periapical regions and periodontal ligament thickness were normal. No inflammatory cells, resorption of mineralized tissue (dentin, cementum, and alveolar bone) or bacteria were observed. The lamina dura was intact and no areas of periapical bone rarefaction or internal/external root resorption were observed radiographically. It can be concluded that Rely X? Unicem and Multilink^® caused no adverse tissue reactions and may be indicated for cementation of indirect restorations in deep dentin cavities without pulp exposure. Microsc. Res. Tech. 78:1098–1103, 2015. © 2015 Wiley Periodicals, Inc.     

Caiman periodontium as an intermediate between basal vertebrate ankylosis-type attachment and mammalian "true" periodontium

The teeth of many fish, amphibia, and reptiles are attached to the alveolar bone via ankylosis. In contrast, mammalian periodontia are characterized by a gomphosis, an attachment of the tooth root in the alveolar bone socket via periodontal ligament fibers. Among the reptiles, the crocodilians are the only group featuring a gomphosis-type connection between tooth root and alveolar bone, while in other reptiles tooth-root and jawbone are connected via ankylosis. The purpose of the present study was to compare several key features of the crocodilian periodontium with those of the mammalian and noncrocodilian reptile periodontium. As experimental models for our study we chose the periodontium of newborn geckos (Hemidacylus turcicus), juvenile caimans (Caiman crocodilus crocodilus), and 10-day-postnatal Swiss-Webster mice (Mus musculus) as representative models for noncrocodilian reptiles, crocodilian reptiles, and mammals. The caiman periodontium emerged as an intermediary between the mineral-free mouse ligament and the mineralized gecko ankylosis-type attachment. Caiman ligament fibers were less organized than mouse ligament fibers but featured distinct fasciae surrounding ligament fiber bundles. Caiman Hertwig's epithelial root sheath (HERS) was similarly perforated as mouse HERS and distinctly different from the continuous gecko HERS. Both caiman and mouse HERS covered the entire tooth root length, while in the gecko HERS was limited to the coronal portion of the root, allowing for cementoid-mediated ankylosis at the apical tip of the root. We interpret our data to indicate distinct differences in mineral distribution, periodontal ligament fiber organization, and HERS distribution between noncrocodilian reptiles, crocodilian reptiles, and mammals. Mineral deposits in the caiman ligament may reflect an evolutionary position of the caiman periodontium between ankylosis and gomphosis.     

Osteoclastic bone resorption around intraosseous screws in rat and pig mandibles

This report describes osteoclastic bone resorption around intraosseous fixation screws in rat and pig mandibles. These screws supported distraction devices and provided for neutral fixation following the distraction period. Progressive clinical instability of bicortical screws and radiographic and histologic evidence of osseous resorption were frequent findings. In rats, clinical evaluation revealed screw loss and/or loosening in 50% of the rats between 11 and 30 days of neutral fixation. Radiographic signs of resorption were apparent around 60% of the screws that were in place at the end of the observation period. The total rate of resorption or loss was 64 of 80 screws (80%). Histologic examination showed partial or extensive osteolysis around the screw holes in 87% of screws that were clinically fixed in the bone at sacrifice. In histologic sections of porcine specimens, osseous resorption around identifiable screw holes was present in 75% of the cases, and showed progressive increase in resorption with time. Osteoclastic resorption was common around bicortical screws that were evaluated after they had served for osseous stability.     

Ultrastructural and immunohistochemical study of the effect of sodium alendronate in the progression of experimental periodontitis in rats

The aim of the present research was to investigate the ultrastructural aspects and the immunoexpression of receptor activator of NFκB ligand (RANKL) and osteoprotegerin (OPG) on experimental periodontal disease of alendronate (ALN)‐treated rats. Male Wistar rats received daily injections of 2.5 mg/kg body weight of ALN during 7 days previously and 7, 14, and 21 days after the insertion of a 4.0 silk suture into the gingival sulcus around the right upper second molar. Specimens were fixed in 0.1% glutaraldehyde + 4% formaldehyde under microwave irradiation, decalcified in 4.13% EDTA and paraffin embedded for TRAP histochemistry and immunohistochemistry for RANKL and OPG, or embedded in Spurr epoxy resin for TEM analysis. ALN reduced the activity of osteoclasts and significantly decreased the resorption of the alveolar crest. In the control group the alveolar crest appeared resorbed by TRAP‐positive osteoclasts, which presented ultrastructural features of activated cells. The immunoexpression of RANKL was not inhibited by the drug; however, the expression of OPG was increased in the treated animals. The alveolar crest of ALN‐treated specimens at 21 days showed signs of osteonecrosis, like empty osteocyte lacunae, the exposed bone regions and bacterial infection. The results showed that ALN treatment in individuals with periodontal disease represents a risk of osteonecrosis because of the reduced activity of osteoclasts resultant of the increased immunoexpression of OPG. Microsc. Res. Tech. 77:902–909, 2014. © 2014 Wiley Periodicals, Inc.     

Time-dependent mechanical behaviour of the periodontal ligament

The process of tooth displacement in response to orthodontic forces is thought to be induced by the stresses and strains in the periodontium. The mechanical force on the tooth is transmitted to the alveolar bone through a layer of soft connective tissue, the periodontal ligament. Stress and/or strain distribution in this layer must be derived from mathematical models, such as the finite element method, because it cannot be measured directly in a non-destructive way. The material behaviour of the constituent tissues is required as an input for such a model. The purpose of this study was to determine the time-dependent mechanical behaviour of the periodontal ligament due to orthodontic loading of a tooth. Therefore, in vivo experiments were performed on beagle dogs. The experimental configuration was simulated in a finite element model to estimate the poroelastic material properties for the periodontal ligament. The experiments showed a two-step response: an instantaneous displacement of 14.10 +/- 3.21 microns within 4 s and a more gradual (creep) displacement reaching a maximum of 60.00 +/- 9.92 microns after 5 h. This response fitted excellently in the finite element model when 21 per cent of the ligament volume was assigned a permeability of 1.0 x 10(-14) m4/N s, the remaining 97 per cent was assigned a permeability of 2.5 x 10(-17) m4/N s. A tissue elastic modulus of 0.015 +/- 0.001 MPa was estimated. Our results indicate that fluid compartments within the periodontal ligament play an important role in the transmission and damping of forces acting on teeth.     

齿轮-转子系统的振动特性分析

根据转子动力学和齿轮啮合的基本原理,建立了考虑陀螺力矩的齿轮转子系统的动力学模型,以此求得齿轮转子啮合刚度矩阵和阻尼矩阵。探讨了啮合刚度、支承刚度对系统固有频率以及系统稳定性的影响。结果表明齿轮的啮合刚度对弯曲振动以及弯扭耦合振动固有频率的影响不大,而当啮合刚度介于2×105~2×108之间时,对弯扭耦合振动的相对稳定性却有较大的影响;另增大支承刚度,固有频率相应提高;减小跨距可以提高系统的稳定性。分析结果对工程应用具有重要的意义。     

单磁耦合式压电振动俘能器的建模与试验

为实现高可靠性及宽频带振动能量的回收,提出了一种单磁耦合式压电振动俘能器。建立了俘能器的动力学方程,采用COMSOL仿真分析了磁铁水平耦合距离d、竖直耦合距离h及耦合角α对势能的影响;设计制作了样机,并进行了试验测试。试验结果表明,俘能器的势能曲线随水平耦合距离d减小由单势阱变为双势阱,且存在较佳的磁铁水平耦合距离（d=11 mm）,使双势阱的阱深适中、俘能器的固有频率减小、有效频带变宽;竖直耦合距离h增大对有效频带的影响较小,h≤2 mm时,相较于无磁耦合（NMC）降低了固有频率;仅改变耦合角α时,存在最佳参数组合（d=14 mm、h=6 mm、α=67.5°）使俘能器获得较低的固有频率（16 Hz）和较宽的有效带宽（19.6 Hz）,较无磁耦合时的有效带宽拓宽了6 Hz,进而提高了俘能器的发电性能。     

Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities

The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild-type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations of specific collagen fragments believed to discriminate between cathepsin K and MMP cleavage. Next, we provide evidence that MMPs are very critical for osteoclast migration, thereby controlling also the cell-matrix interactions required for cell attachment/detachment. The evidence supporting this role is based on a model of osteoclast recruitment in primitive long bones, an assay of osteoclast invasion through collagen gel, and the effect of proteinase inhibitors/knockouts in these models. Furthermore, we mention observations indicating a role of MMPs in initiation of bone resorption. Finally, we emphasize the many distinct ways MMPs may alter focally the extracellular environment thereby regulating the osteoclast behavior. Although the understanding of MMPs in osteoclast biology is rapidly expanding, it is suspected that important roles remain to be discovered.     

The effect of primary stability on load transfer and bone remodelling within the uncemented resurfaced femur

One of the major causes of aseptic loosening in an uncemented implant is the lack of any attachment between the implant and the bone. The implant's stability depends on a combination of primary stability (mechanical stability) and secondary stability (biological stability). The primary stability may affect the implant-bone interface condition and thus influence the load transfer and mechanical stimuli for bone remodelling in the resurfaced femur. This paper reports the results of a study into the affect of primary stability on load transfer and bone adaptation for an uncemented resurfaced femur. Three-dimensional finite element models were used to simulate the intact and resurfaced femurs and the bone remodelling. As a first step towards assessing the immediate post-operative condition, a debonded interfacial contact condition with varying levels of the friction coefficient (0.4, 0.5, and 0.6) was simulated at the implant-bone interface. Then, using a threshold value of micromotion of 50 microm, the implant-bone interfacial condition was varied along the implant-bone boundary to mechanically represent non-osseointegrated or osseointegrated regions of the interface. The considered applied loading conditions included normal walking and stair climbing. Resurfacing leads to strain shielding in the femoral head (20-75 per cent strain reductions). In immediate post-operative conditions, there was no occurrence of elevated strains in the cancellous bone around the proximal femoral neck-component junction resulting in a lower risk of neck fracture. Predominantly, the micromotions were observed to remain below 50 microm at the implant-bone interface, which represents 97-99 per cent of the interfacial surface area. The predicted micromotions at the implant-bone interface strongly suggest the likelihood of bone ingrowth onto the coated surface of the implant, thereby enhancing implant fixation. For the osseointegrated implant-bone interface, the effect of strain shielding was observed in a considerably greater bone volume in the femoral head as compared to the initial debonded interfacial condition. A 50-80 per cent peri-prosthetic bone density reduction was predicted as compared to the value of the intact femur, indicating bone resorption within the superior resurfaced head. Although primary fixation of the resurfacing component may be achieved, the presence of high strain shielding and peri-prosthetic bone resorption are a major concern.     

垂直型多级位移放大机构设计与力学解析建模

针对压电位移放大机构在垂直方向较难实现大行程、高频带宽度的问题,结合两个复合菱形机构、两个杠杆机构以及一个普通菱形机构,提出了一种垂直型多级位移放大机构。基于能量守恒方法和弹性梁理论建立了位移放大比和输入/输出刚度解析模型,根据拉格朗日方程推导了固有频率解析模型。通过有限元法对解析模型进行了验证,所建立的位移放大比解析模型有较高的预测精度,可为大行程垂直型柔顺平台的优化设计提供参考。与文献中的位移放大机构性能对比结果表明,提出的垂直型位移放大机构具有更好的静动态平衡性能,其位移放大比可达43.29,同时保持一个较高的固有频率561.28 Hz。     

Histological evaluation on bone regeneration of dental implant placement sites grafted with a self-setting alpha-tricalcium phosphate cement

This study aimed to evaluate the histological characteristics of the new bone formed at dental implant placement sites concomitantly grafted with a self-setting tricalcium phosphate cement (BIOPEX-R). Standardized defects were created adjacent to the implants in maxillae of 4-week-old male Wistar rats, and were concomitantly filled with BIOPEX-R. Osteogenesis was examined in two sites of extreme clinical relevance: (1) the BIOPEX-R-grafted surface corresponding to the previous alveolar ridge (alveolar ridge area), and (2) the interface between the grafting material and implants (interface area). At the alveolar ridge area, many tartrate-resistant acid phosphatase (TRAPase)-reactive osteoclasts had accumulated on the BIOPEX-R surface and were shown to migrate toward the implant. After that, alkaline phosphatase (ALPase)-positive osteoblasts deposited new bone matrix, demonstrating their coupling with osteoclasts. On the other hand, the interface area showed several osteoclasts initially invading the narrow gap between the implant and graft material. Again, ALPase-positive osteoblasts were shown to couple with osteoclasts, having deposited new bone matrix after bone resorption. Transmission electron microscopic observations revealed direct contact between the implant and the new bone at the interface area, although few thin cells could still be identified. At both the alveolar ridge and the interface areas, newly formed bone resembled compact bone histologically. Also, concentrations of Ca, P, and Mg were much alike with those of the preexistent cortical bone. In summary, when dental implant placement and grafting with BIOPEX-R are done concomitantly, the result is a new bone that resembles compact bone, an ideal achievement in reconstructive procedures for dental implantology.     

Differentiation and functions of osteoclasts and odontoclasts in mineralized tissue resorption

The differentiation and functions of osteoclasts (OC) are regulated by osteoblast-derived factors such as receptor activator of NFKB ligand (RANKL) that stimulates OC formation, and a novel secreted member of the TNF receptor superfamily, osteoprotegerin (OPG), that negatively regulates osteoclastogenesis. In examination of the preosteoclast (pOC) culture, pOCs formed without any additives expressed tartrate-resistant acid phosphatase (TRAP), but showed little resorptive activity. pOC treated with RANKL became TRAP-positive OC, which expressed intense vacuolar-type H(+)-ATPase and exhibited prominent resorptive activity. Such effects of RANKL on pOC were completely inhibited by addition of OPG. OPG inhibited ruffled border formation in mature OC and reduced their resorptive activity, and also induced apoptosis of some OC. Although OPG administration significantly reduced trabecular bone loss in the femurs of ovariectomized (OVX) mice, the number of TRAP-positive OC in OPG-administered OVX mice was not significantly decreased. Rather, OPG administration caused the disappearance of ruffled borders and decreased H(+)-ATPase expression in most OC. OPG deficiency causes severe osteoporosis. We also examined RANKL localization and OC induction in periodontal ligament (PDL) during experimental movement of incisors in OPG-deficient mice. Compared to wild-type OPG (+/+) littermates, after force application, TRAP-positive OC were markedly increased in the PDL and alveolar bone was severely destroyed in OPG-deficient mice. In both wild-type and OPG-deficient mice, RANKL expression in osteoblasts and fibroblasts became stronger by force application. These in vitro and in vivo studies suggest that RANKL and OPG are important regulators of not only the terminal differentiation of OC but also their resorptive function. To determine resorptive functions of OC, we further examined the effects of specific inhibitors of H(+)-ATPase, bafilomycin A1, and lysosomal cysteine proteinases (cathepsins), E-64, on the ultrastructure, expression of these enzymes and resorptive functions of cultured OC. In bafilomycin A1-treated cultures, OC lacked ruffled borders, and H(+)-ATPase expression and resorptive activity were significantly diminished. E-64 treatment did not affect the ultrastructure and the expression of enzyme molecules in OC, but significantly reduced resorption lacuna formation, by inhibition of cathepsin activity. Lastly, we examined the expression of H(+)-ATPase, cathepsin K, and matrix metalloproteinase-9 in odontoclasts (OdC) during physiological root resorption in human deciduous teeth, and found that there were no differences in the expression of these molecules between OC and OdC. RANKL was also detected in stromal cells located on resorbing dentine surfaces. This suggests that there is a common mechanism in cellular resorption of mineralized tissues such as bone and teeth.     

焦炭塔结构的固有频率和振型研究

在传统的直立塔设备固有频率和振型的计算中,将塔设备简化为悬臂梁计算模型,但实际塔的薄壁圆筒结构与梁模型不符,为此对焦炭塔建立有限元分析模型进行模态分析,得到焦炭塔的固有频率和振型,计算分析表明,由于焦碳塔特殊的结构特点使得焦炭塔的振动特性与传统大型直立设备简化为悬臂梁计算模型所得振动特性相比有所不同,因此焦炭塔结构的计算中涉及到高阶振型与固有频率时,不宜简化为悬臂梁计算模型。     

大间隙环流中刚支转子系统振动特性研究

基于Myklestad传递矩阵法．建立了大间隙环流中转子系统的运动方程，采用数值方法分析转子系统的振动特性。数值计算结果表明，由于大间隙环流的流固耦合作用，使转子系统的固有频率、阻尼临界转速、稳定性和不平衡响应均发生了不同程度的变化。数值计算结果与已有的解析分析和实验结果有较好的一致性。     

The role of periodontal disease in atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (ASCVD) includes a group of disorders of the heart and blood vessels and accounts for major morbidity and premature death worldwide. Periodontitis is a chronic inflammatory disease with the gradual destruction of supporting tissues around the teeth, including gingiva, periodontal ligament, alveolar bone, and cementum. Periodontitis has been found to potentially increase the risk of ASCVD. Generally, oral microorganisms and inflammation are the major factors for periodontitis to the incidence of ASCVD. Recently, evidence has shown that the loss of masticatory function is another important factor of periodontitis to the incidence of ASCVD. In this review, we illustrate the recent finding of the relationship between periodontitis and ASCVD, from a microscale perspective-oral microorganisms, inflammation, and tooth loss. With the high prevalence of periodontitis, it is important to add oral therapy as a regular ASCVD prevention strategy. Regular dental visits could be a helpful strategy for ASCVD patients or general medical practitioners.