Mandibular bone remodeling induced by dental implant

The ability to assess the effects of an implant on bone remodeling is of particular importance to prosthesis placement planning and associated treatment assurance. Prediction of on-going bone responses will enable us to improve the performance of a restoration. Although the bone remodeling for long bones had been extensively studied, there have been relatively few reports for dental scenarios despite its increasing significance with more and more dental implant placements. This paper aimed to develop a systematic protocol to assess mandibular bone remodeling induced by dental implantation, which extends the remodeling algorithms established for the long bones into dental settings. In this study, a 3D model for a segment of a human mandible was generated from in vivo CT scan images, together with a titanium implant embedded to the mandible. The results examined the changes in bone density and stiffness as a result of bone remodeling over a period of 48 months. Resonance frequency analysis was also performed to relate natural frequencies to bone remodeling. The density contours are qualitatively compared with clinical follow-up X-ray images, thereby providing validity for the bone remodeling algorithm presented in dental bone analysis.     

Growth of bones as revealed by implant markers in animals

Implantation of screws, pegs, wires, or other material as markers has been of value during the last 200 years in the serial study of growth of bones. With this direct method, for a given period, the increase in distance between implants on either side of an endochondral growth center or suture can be readily determined. In contrast, the relatively constant position of two or more implants within a single bone can be utilized to establish the pattern of peripheral apposition and resorption. When radiopaque implants are used in combination with serial roentgenography, not only the amount but also the rate, periods of activity and relative direction of growth may be determined. This indirect method obviates reoperating or killing the animal to measure the distance between implants. Some of the problems in the use of these methods are that (1) growth occurs in more than one plane, (2) the implants may not remain where inserted into the bone, (3) the implants may not be in a plane parallel to the X -ray film, and (4) the distance between the implants and the film may not be constant. (Abstract previously published Am. J. Phys. Anthrop., 27: 236, September, 1967).     

Application of the finite element method in dental implant research

This article provides a review of the achievements and advancements in dental technology brought about by computer-aided design and the all powerful finite element method (FEM) of analysis. The scope of the review covers dental implants, jawbone surrounding the implant and the biomechanical implant and jawbone interaction. Prevailing assumptions made in the published finite element analysis (FEA) and their limitations are discussed in some detail which helps identify the gaps in research as well as future research direction.     

Proliferative effects of angiotensin II and endothelin-1 on guinea pig gingival fibroblast cells in culture

We investigated whether phenytoin (PHT) and nifedipine (NIF) induce angiotensin II (Ang II) and endothelin-1 (ET-1) generation by cultured gingival fibroblasts derived from guinea pigs and whether Ang II and ET-1 induce proliferation of these cells. Immunohistochemical experiments showed that PHT (250 nM) and NIF (250 nM) increased the immunostaining intensities of immunoreactive Ang II and ET-1 (IRET-1) in these cells. Captopril (3 microM), an angiotensin-converting enzyme inhibitor, reduced these enhanced intensities to control levels. Ang II (100 nM) enhanced the immunostaining intensity of IRET-1. PHT (250 nM) and NIF (250 nM)-induced cell proliferation. Both PHT- and NIF-induced proliferation was inhibited by captopril (3 microM). Ang II (100 nM) and ET-1 (100 nM) also induced cell proliferation. Ang II-induced proliferation was inhibited by CV11974 (1 microM), an AT(1) receptor antagonist and saralasin (1 microM), an AT(1)/AT(2) receptor antagonist, but not by PD123,319 (1 microM), an AT(2) receptor antagonist. ET-1-induced proliferation was inhibited by BQ123 (10 microM), an ET(A) receptor antagonist, but not by BQ788 (1 microM), an ET(B) receptor antagonist. These findings suggest that PHT- and NIF-induced gingival fibroblast proliferation is mediated indirectly through the induction of Ang II and ET-1 and probably mediated through AT(1) and ET(A) receptors present in or on gingival fibroblasts.     

Histological and biomechanical studies of hydroxylapatite implant.

Bony defects measuring 12x12x12 millimeters in size were created bilaterally over the proximal end of the femurs of 10 Macaca cyclopis monkeys and implanted with particulate hydroxylapatite. The animals were sacrificed according to a predetermined sequence of post-operative 1, 2, 3, 6, and 8 months. The specimens taken from the implant sites in the two femurs of each animal were chosen randomly either for histological observation or for compressive strength tests under vertical loads. Histological pictures showed only loose fibrous tissue over the interparticular space of the implant site at the first month after surgery. Woven bone could be observed over the basal part of the implant site at the second month. New bone formed over the central part of the implant site at the third month after surgery. Continuing maturation of the bone tissue could be observed over the interparticular space of the implant site until the late stages at the 6th and 8th month after surgery. The results of compressive strength tests were compatible with the histological observations. The value of the elastic modulus was low initially at the first month, but increased gradually with time due to organization of fibrous tissue, condensation of HA particles, and ossification as well as maturation of bone tissue. The value of elastic modulus at the third month was equal to that of cortical bone tissue and even two-fold higher than that of the cortical bone at the eighth month after surgery. These results provide valuable information about the compressive strength of the HA implant in host tissue.     

Characterization of Actinomyces species isolated from failed dental implant fixtures

In the oral cavity, Actinomyces form a fundamental component of the indigenous microflora, being among initial colonizers in polymicrobial biofilms. However, some differences may exist between different species in terms of their attachment not only to teeth but also to biomaterials. In this study we investigated the distribution of Actinomyces in 33 dental implant fixtures explanted from 17 patients. The identification was based on comprehensive biochemical testing and gas-liquid chromatography and when needed, 16S rRNA sequencing. Actinomyces was the most prevalent bacterial genus in these failed implants, colonizing 31/33 (94%) of the fixtures. Proportions of Actinomyces growth of the total bacterial growth in the Actinomyces-positive fixtures varied from 0.01% up to 75%. A. odontolyticus was the most common Actinomyces finding, present in 26/31 (84%) Actinomyces-positive fixtures. Actinomyces naeslundii and A. viscosus were both detected in 10/31 (32%) and A. israelii in 7/31 (23%) fixtures. Other Actinomyces species, including A. georgiae, A. gerencseriae and A. graevenitzii, were detected less frequently. Our results suggest that Actinomyces species are frequent colonizers on failed implant surfaces, where A. odontolyticus was the far most prominent Actinomyces species.     

A three dimensional finite element study on dental implant design

Implant diameter and length are the most effective parameters affecting stress distribution in surrounding bones. In order to extract simplified design equations to better understand implants behavior, 25 different implant designs with gradual increase in diameter and length were analyzed in 3D using Finite Element Method. Four types of loadings were applied on each design: tension of 50 N, compression of 100 N, bending of 20 N, and torque of 2 Nm to derive design curves.Analysis of results showed that increasing implant diameter and length generate better stress distribution on spongy and cortical bones. Approximate design equations and curves were obtained as a result of this study.     

Heterozygosity effects in studies of genetic markers and disease

Examples were discussed where heterozygosity was associated with increased or decreased disease risks and where the apparent mechanism is direct functional involvement of gene products and not linkage disequilibrium. Special attention was paid to the impact of Hp (haptoglobin) heterozygosity on a number of different multifactorial disorders. When phenotype distributions in patients show large deviations from the Hardy-Weinberg equilibrium significant differences between patients and controls may be found concerning phenotype distributions but not with respect to the frequencies of alleles and phenotypic factors. The common method of studying ratios of phenotypic factors by pooling homo- and heterozygotes is in principle a conservative approach which tends to underestimate the strength of associations and to obscure heterozygosity effects. A significant deviation from the Hardy-Weinberg equilibrium in a marker system examined in a group of patients is in itself a sensitive indicator of phenotypic association with the disease in question.     

Molecular markers in genetic and selection studies of maize

The review represents the literature data and the data of personal research demonstrating the modern achievements in molecular-genetic analysis of maize (Zea mays L.). The importance of the use of DNA-technologies in genetics, breeding and seed-production of maize is shown. The examples of application of molecular-genetic markers in breeding process to increase its efficacy are demonstrated.     

Ranking prognosis markers in cancer genomic studies

In cancer research, high-throughput genomic studies have been extensively conducted, searching for markers associated with cancer diagnosis, prognosis and variation in response to treatment. In this article, we analyze cancer prognosis studies and investigate ranking markers based on their marginal prognosis power. To avoid ambiguity, we focus on microarray gene expression studies where genes are the markers, but note that the methodology and results are applicable to other high-throughput studies. The objectives of this study are 2-fold. First, we investigate ranking markers under three commonly adopted semiparametric models, namely the Cox, accelerated failure time and additive risk models. Data analysis shows that the ranking may vary significantly under different models. Second, we describe a nonparametric concordance measure, which has roots in the time-dependent ROC (receiver operating characteristic) framework and relies on much weaker assumptions than the semiparametric models. In simulation, it is shown that ranking using the concordance measure is not sensitive to model specification whereas ranking under the semiparametric models is. In data analysis, the concordance measure generates rankings significantly different from those under the semiparametric models.     

Plasminogen activator inhibitor type 1 expression induced by lipopolysaccharide of Porphyromonas gingivalis in human gingival fibroblast

In the gingival tissues of patients with periodontitis, inflammatory responses are mediated by a wide variety of genes. In our previous screening study, plasminogen activator inhibitor type 1 (PAI-1) mRNA binding protein expression was increased in gingiva from periodontitis patients. In this study, we further investigated the signaling pathway involved in PAI-1 expression induced by Porphyromonas gingivalis LPS (Pg LPS) in human gingival fibroblasts (HGF). When HGFs were treated with Pg LPS, both PAI-1 mRNA expression and PAI-1 protein were induced in a dose-dependent manner. Pg LPS induced NF-κB activation and the expressions of PAI-1 mRNA and protein were suppressed by pretreating with a NF-κB inhibitor. Pg LPS also induced ERK, p38, and JNK activation, and Pg LPS-induced PAI-1 expression was inhibited by ERK/p38/JNK inhibitor pretreatment. In conclusion, Pg LPS induced PAI-1 expression through NF-κB and MAP kinases activation in HGF.     

Immunohistochemical and gene expression analysis of stem-cell-associated markers in rat dental pulp

Stem cells in the dental pulp comprise rare populations lacking definitive cytological markers and thus are poorly characterized in vivo, especially in rat species. To gain more insight into the phenotypical characteristics and tissue distribution of these cells, we examined the distribution of stem-cell-associated marker-expressing cells and mRNA expression levels of stem-cell-associated markers in the rat molar. CD146-positive cells co-expressing microtubule-associated protein 1B were counted following double-labeling immunoperoxidase staining and their density in the coronal pulp, root pulp and periodontal ligament was compared. Moreover, mRNA expression levels of CD146, CD105, CD166 and secreted phosphoprotein 1 (SPP1; also known as osteopontin, a negative regulatory element of the stem cell niche) were analyzed in these regions by using real time polymerase chain reaction. The double-positive cells could be clearly distinguished from non-stem cells single-stained by either of the markers and showed a significantly higher density in the coronal pulp compared with the other regions (P<0.05). Moreover, mRNA expression levels of CD146, CD105 and CD166 were significantly higher in the coronal pulp than in the other regions (P<0.05). On the other hand, SPP1 mRNA expression was significantly higher in the periodontal ligament than in the pulp. Thus, the density of stem-cell-associated marker-expressing cells and stem-cell-associated gene expression levels are higher in the coronal pulp than in the root pulp and periodontal ligament, suggesting that the coronal pulp harbors more stem cells than the other regions.     

Osteoblast physiology in normal and pathological conditions

Osteoblasts are mononucleated cells that are derived from mesenchymal stem cells and that are responsible for the synthesis and mineralization of bone during initial bone formation and later bone remodelling. Osteoblasts also have a role in the regulation of osteoclast activity through the receptor activator of nuclear factor κ-B ligand and osteoprotegerin. Abnormalities in osteoblast differentiation and activity occur in some common human diseases such as osteoporosis and osteoarthritis. Recent studies also suggest that osteoblast functions are compromised at sites of focal bone erosion in rheumatoid arthritis.     

Spatial development of gingival fibroblasts and dental pulp cells: Effect of extracellular matrix

Cells sensing changes in their microenvironmental stiffness and composition alter their responses, accordingly. This study determines whether gingival fibroblasts (GFs) and dental pulp mesenchymal stem cells (DPMSCs) support the formation of continuous layers in vitro by mimicking the stiffness and protein composition of their native extracellular matrix (ECM). Immortalized cells were incubated with (i) 0–100% Matrigel-ECM (M-ECM) for 7-28d, and with (ii) collagen and fibrin matrices for 14d. Cultures were analyzed by phase-contrast, fluorescence and confocal microscopies. The diameters and surface areas were measured via ImageJ. Self-renewal markers were detected by RT-PCR and immunocytochemistry assays. GFs and DPMSCs developed spheroids interconnected by elongated cell bundles or layers, respectively, expressing the self-renewal markers. Increased matrix stiffness resulted in spheroids replacement by the interconnecting cells/layers. Both cells required 100% M-ECM to reduce their spheroid diameter. However, it reduced the surface area of the interconnecting layers. Those differences led to extended, spindle-shaped GFs vs. compact, ring-shaped DPMSCs constructs. Collagen and fibrin matrices developed continuous layers of tightly connected cells vs. distinctive scattered cell aggregates, respectively. The ability of GFs and DPMSCs to create tissue-like multicellular layers at various matrix conditions may be imprinted by cells’ adaptation to mechanical forces and composition in vivo.     

In vitro carcinogenesis studies on mouse fibroblast cells

Fibroblast cell lines were established from pulmonary explants derived from inbred CBA T6T6 mouse embryos. Cell lines controlled for the absence of spontaneous transformation were treated with 20=methylcholenthrene (0, 1 microgram/ml). The altered biological characteristics were studied during the process of the malignant transformation by the comparison of the untreated and 20-methylcholanthrene pretreated cell populations: the loss of contact inhibition and the connection between the malignant transformation and the arylhydrocarbon hydroxylase enzyme activity were investigated. No changes in the cell proliferation rate could be found following malignant transformation, but an increased resistance against altered circumstances was observed. In the course of passages, a gradual decreases in aryl hydrocarbon hydroxylase activity of the untreated line was seen, which disappeared or significantly decreased following 20-methylcholanthrene treatment, compared to the controls.