RSS 1.0Dental College of Georgia
Since the graduation of its first class in 1973, the Dental College of Georgia - the State‘s sole dental school and one of only 56 in the entire United States - has demonstrated an exemplary record of protecting the oral health of our State’s residents. The Dental College of Georgia was formerly known as the School of Dentistry.
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This Community contains the Department of Continuing Dental Education Publications, the Department of Oral Biology Faculty Papers, the Department of Oral Rehabilitation Faculty Papers, and the Department of Periodontics Faculty Papers.
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SYNERGISTIC EFFECTS OF THE COMBINATION OF ERLOTINIB & EXO2 ON HEAD AND NECK CANCERMore than 90% of head and neck cancer is head and neck squamous cell carcinoma1 (HNSCC). Currently, the treatment involves modern surgery, conventional chemotherapy, and radiation. However, targeting, the epidermal growth factor receptor (EGFR) has been shown to prove advantageous for patient survival. EGFR activation leads to cell cycle progression. Blocking the EGFR by an antibody results in the inhibition of the receptor, therefore inhibition of cell proliferation. This makes EGFR a prime target for anticancer therapy, specifically with tyrosine kinase inhibitors being looked at as a possible form of inhibition. The goal of this project was to hopefully use small molecule inhibitor EXO2 and an EGFR specific tyrosine kinase inhibitor, Erlotinib, in a synergistic manner to fight against HNSCC. This study was done using cell cultures, MTT assay�s and western blot techniques, with cell cultures being done using the H6 cell line. The results from this study were found to be a preliminary success and will pave the way for future experiments in this area.
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SERUM-C TERMINAL CROSSLINKING TELOPEPTIDE (CTX) AS A PREDICTIVE BIOMARKER OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF JAW (BRONJ): SYSTEMATIC REVIEW AND META-ANALYSISThe aim of this systematic review was to evaluate the validity of using preoperative serum C-terminal crosslinking telopeptide (CTX) levels as predictive factor of increased risk of developing medication-related osteonecrosis of the jaw (MRONJ) in patients on bisphosphonate (BP) therapy who undergo invasive dental procedures. A search was conducted through PubMed, MEDLINE, and Web of Science, following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was conducted on the risk ratio. The methodological index for nonrandomized studies (MINORS) and Quality Appraisal of Reliability Studies (QAREL) checklist were used to assess quality. Eighteen clinical trials, involving 2301 patients were included. Most patients received Alendronate or Risedronate for an average of 62.14 months. The average serum CTX level in BP-treated patients before surgery was 217.67 pg/ml. Meta-analysis demonstrated that the cutoff in CTX level (150 pg/ml) was not predictive of BRONJ risk. The sensitivity of CTX value <150 pg/ml was 34.26% and the specificity was 77.08%. The use of CTX to diagnose BRONJ risk following dental procedures in bisphosphonate-treated patients is not justified. Further studies are needed to develop other reliable biomarkers.
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Histology of the Dental Extraction Sites of Bisphosphonate Treated RatsBisphosphonate is a drug given to both men and women who are experiencing decreasing bone density and strength. When patients taking bisphosphonate undergo some sort of jaw trauma (i.e. tooth extraction, accident), they can experience necrosis or cell death of the jawbone. Our hypothesis is that bisphosphonate molecules bound to the bone matrix contribute to bone necrosis. For my thesis, a histological analysis of the mandibles from bisphosphonate treated rats after dental extraction with and without removal of bisphosphonates from the extraction site of the bone was done. Histological sections of the jaw from bisphosphonate treated rats after bilateral extraction of the first and second molar teeth were taken. On one side, the extraction site was treated with EDTA to chelate bisphosphonates from the bony wall of the tooth socket. The other side of the rat’s jaw was treated with Saline. I then evaluated the vitality of alveolar bone by counting the number of dead versus live osteocytes around the extraction site and comparing the ratios between the chelated and un-chelated sides from each rat. The study determined whether removal of localized bisphosphonates is beneficial to preserve bone vitality after dental extraction. As expected, the percentage of live osteocytes decreased in the alveolar bone of animals treated with Zoledronate (ZA), a strong dose of bisphosphonate. Furthermore, there was a trend of increased percentage of live cells when EDTA was used, although the differences were not statistically significant. These results support other studies in our laboratory that have shown that localized bisphosphonates play a role in the osteonecrosis associated with ZA treatment. It, therefore, provides evidence that localized bisphosphonates contribute to the etiology of bone necrosis in patients undergoing bisphosphonate treatment.
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Correlation of Deph of Solvent Resistance with Monomer ConversionIn the mouth, inadequately cured dental restorative materials may lead to detrimental consequences in their longevity. As light travels through these photo-curable restorative composites, there is an exponential decrease in light penetration with depth, and therefore the extent of local polymerization is compromised. This phenomenon is termed the “Depth of Cure” issue, which restricts the thickness if increment that each restorative material can be placed and polymerized. The purpose of this research is to develop an easily performed test that provides a correlational value between visually identifiable transition zones within acetone-sonicated, sectioned, cured composite specimens and the extent to which a composite has reached maximal monomer conversion values, to ultimately determine adequacy of polymerization at the depth of cure for certain restorative materials. This test method, proven to be independent of composite type, will be submitted to the working group associated with the revision of the International Organization for Standards Organization 4049 standard, for consideration of further testing and perhaps replacement of the current method. This research provides a fulfillment of the requests from well-respected dental clinicians to provide a clinically relevant and meaningful depth of cure test.
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Marker Co-Expression Analysis of Initial Cellular Events in the Critical-Size Rat Calvarial Defect Model and the Effect of Bone Morphogenetic Protein-2 (rhBMP-2)Craniofacial defects can result from congenital malformations, trauma, tumor resection,periodontal disease, post-extraction ridge remodeling, and peri-implantitis. Regenerationof bone is critical to achieving functional and esthetic outcomes in the rehabilitation ofsuch defects. Traditional strategies for osseous regeneration include a multiple ofsurgical techniques utilizing autologous bone, cadaver-sourced allogeneic or xenogeneicbone, synthetic bone biomaterials, barrier membranes, or combinations thereof(Wikesjö, Qahash 2009). The need to enhance the predictability of regeneration inespecially large defects that cannot heal adequately without intervention (critical-sizedefects) has led to recent development of protein- and cell-based technologies.[Introduction, first paragraph]
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Changes in the RANK/RANKL/OPG Signaling System as a Mechanism of Zoledronate-Induced Osteonecrosis of the JawBisphosphonates (BPs) are widely used for the treatment of osteoporosis, hypercalcemia of malignancy, skeletal-related events associated with bone metastases, and for managing lytic lesions of multiple myeloma. A serious risk associated with the use of BPs is the development of Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ), a painful and inflamed area of exposed bone in the oral cavity that fails to heal after 6-8 weeks. The cause of BRONJ is unknown, but it is believed to be due primarily to a longterm suppression of bone remodeling, caused by BP’s potent inhibition of osteoclastic activity. At the cellular level, it is generally accepted that bisphosphonates are taken in by osteoclasts at sites of relatively greater bone remodeling, owing to the strong affinity of bisphosphonates for the mineralized matrix and the increased activity of osteoclasts at active sites of resorption. The accumulation of intracellular bisphosphonates ultimately leads to osteoclast dysfunction or apoptosis through the formation of nonhydrolyzable ATP-analogues, or due to inhibition of the mevalonate pathway responsible for synthesis of sterols and lipids necessary for proper cellular membrane structure. However, the refined details of the pathophysiology of BRONJ remain elusive. The RANK/RANKL/OPG system is a well-known signaling pathway for the recruitment and differentiation of osteoclasts. RANK is a surface-bound receptor on osteoclasts, and requires binding of its ligand, RANKL, for cell activation and ultimately resorption of bone. On the other hand, OPG is a soluble decoy receptor for RANKL. Therefore, osteoclastic activity is effectively regulated by the ratio of RANKL to OPG. For years, it has been generally accepted that osteoblasts are the primary source of both RANKL and OPG. However, it is now recognized that the master orchestrator of bone activity, the osteocyte, contributes to the pathway. Furthermore, it has been shown that in localized tissue damage or hypoxia, such as in a dental extraction, immediately adjacent surviving nonapoptotic osteocytes upregulate RANKL and downregulate OPG. It is unknown to what extent BPs may alter the normal osteocyte response to injury and hypoxia or, ultimately, the dynamics of the RANK/RANKL/OPG system. Furthermore, the extent to which this could contribute to the development of BRONJ is unexplored.There is a paucity of studies concerning how the fundamental system responsible for bone remodeling, RANK/RANKL/OPG, is effected by BPs. It may be that changes in this system, especially in signals derived from the osteocyte, contribute to the pathophysiology of BRONJ.
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Effect of an Er,Cr:YSGG Laser on P. Gingivalis-Contaminated Titanium Alloy Dental Implant Surfaces In VitroImplant dentistry has become a widely accepted modality to replace missing teeth. However, dental implants are susceptible to biofilm-mediated inflammatory lesions (peri-implant mucositis / peri-implantitis), similar to that seen around natural teeth (gingivitis / periodontitis). These lesions, in turn, threaten the longevity of implants as anchors for dental prostheses. Because of the similarity in etiology and presentation, comparable treatment modalities are applied to resolve peri-implant and periodontal inflammatory lesions. Such a shared treatment includes mechanical debridement, with or without surgical repositioning of the soft tissue complex. However, most contemporary dental implants feature threads to engage the alveolar bone and a micro/nano-textured surface to stimulate bone-implant contact (osseointegration). Therefore, when the implant threads become exposed and contaminated by biofilm, subsequent surface debridement / decontamination becomes considerably more complex than with that of a natural tooth, which is usually debrided using a metal curette or ultrasonic device. The micro/nano-textured surface of a dental implant is easily damaged by instrumentation using a metal curette. If an efficient method of dental implant surface decontamination could be established, then clinical protocols may be developed that effectively clean the implant surface to achieve peri-implant tissue health. To this end, lasers have been introduced; however, directly applied laser energy may also affect implant surface characteristics, including micro/nano-structure and composition, essential to osseointegration. Therefore, lasers may have disadvantageous clinical effects, in turn compromising peri-implant tissue consolidation and health: the very aspects its use is attempting to provide. Commercially available Er,Cr:YSGG lasers have been used to remove such implant-attached deposits, however the efficacy in removal of bacteria and the safety to the implant surface integrity have yet to be demonstrated quantitatively.
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Plasma Membrane Disruption in Orthodontic Tooth Movement(Introduction) One hundred years ago, in 1900, Dr. Edward H. Angle and a dozen colleagues came together to establish dentistry's first specialty, which is known today as orthodontics and dentofacial orthopedics. Orthodontics is a science and an art. It is the art o f creating healthy, beautiful smiles by moving teeth with precise, gradual force expertly applied, and the science concerned with the study o f the growth o f the craniofacial complex, the development o f occlusion and the treatment o f dentofacial abnormalities. Mechanical forces exerted on tooth roots and transmitted to the periodontal tissues initiate the remodeling activity that facilitates the movement o f teeth through bone. The specific changes in the bone surrounding the root o f an orthodontically moved tooth are characterized as resorption and deposition. Resorption o f bone is seen on the compression side o f the tooth. In contrast, bone is deposited in the tension side of the tooth that is being moved in the opposite direction. The biologic response to sustained force against the teeth is a function o f force magnitude; forces great enough to occlude blood vessels lead to pain, sterile necrosis and a process described as undermining resorption that inevitably leads to a delay in tooth movement. Lighter forces allow activation o f osteoclasts, and thus the removal of bone from the compression side by the painless process o ffrontal resorption. Clinicians face the challenge o f maintaining tissue vitality by avoiding undermining resorption, while applying forces heavy enough to produce frontal resorption. An understanding of the cellular and molecular mechanisms that enable bone to adapt to changes in its mechanical environment is important for solving the different challenges o f clinical orthodontics. Almost a century of research has been devoted to examining this phenomenon by morphologic methods. The histologic changes have consequently been well documented, but there are many unanswered questions that must be addressed in order to explain how mechanical deformation is transduced into a desirable biologic response. The aim o f the present investigation was to characterize a novel cellular mechanism for uptake and release of molecules important in bone remodeling by periodontal ligament cells. Specifically, the plasma membrane disruption theory was examined in light o f its role in mechanotransduction in orthodontic tooth movement. These are the first studies linking the placement o f mechanical loading, as occurs in orthodontic tooth movement, with plasma membrane disruption and resealing of periodontal ligament cells. The release o f bFGF and II-ip from the cells of the periodontal ligament was also examined following application o f in vivo strain.
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The Effect of Leucite Crystallization and Thermal History on Thermal Expansion Measurements of Dental PorcelainsObjectives. Measurement of thermal expansion in glassy materials is complicated by thermal history effects. The purpose of this research was to determine whether the occurrence of structural relaxation in glassy materials, such as dental porcelains, an changes in porcelain leucite content could interfere with the accurate measurement of the coefficient of thermal expansion during the thermal expansion measurement itself. Methods. In a randomized design, thermal expansion specimens were fabricated using six commercial body porcelains and the leucite-containing Component No. 1 frit (Weinstein et al. patent, 1962), and subjected to one of the following heat treatments: a single heating run at 3°C/min in a conventional dilatometer followed by air quenching; three successive low-rate heating and cooling thermal expansion runs at 3°C/min in a conventional dilatometer; or three successive high-rate heating and cooling thermal expansion runs at 600°C/min in a laser dilatometer. The remaining specimens were left untreated and served as controls. Potential changes in porcelain leucite content were monitored via quantitative X-ray diffraction. Thermal expansion data for each run over a temperature range of 25-500°C and the leucite content of all specimens were subjected to repeated measures analysis o f variance. Results. The thermal expansion coefficient measured on first slow heating was significantly lower than the values for succeeding low-rate heating and cooling runs in all materials (p < 0.001). The high-rate thermal expansion coefficient obtained on first heating was not significantly different from the values of succeeding heat and cool runs in all materials (p > 0.0S). No significant effect of dilatometer thermal treatments on leucite content (p > 0.05) was shown for all materials studied using both dilatometers. Significance. The crystallization of additional amounts of leucite during thermal expansion runs can be ruled out as a possible interference in the determination of the thermal expansion coefficient of dental porcelain. Conventional dilatometer measurements exhibited structural relaxation during the first heating run, as evidenced by the significant difference between the first heating and subsequent runs, while the laser dilatometer measurements were not affected by this thermal history effect. Therefore, high-rate dilatometry provides a more accurate thermal expansion measurement that is free of interference from structural relaxation and additional leucite crystallization.
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Primary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogsVery often, delayed reconstruction becomes the setting of choice in the reconstruction of large segmental defects in the mandible. Our hypothesis is that rhBMP2 delivery would elicit endogenous expression of BMP2 and VEGF in the soft tissue bed of the defect. Such response is expected to be more pronounced in the immediate than the delayed reconstruction, which will correlate with the quantity and quality of bone formation in the two settings. We also hypothesized that vascular endothelial cells (ECs) of the surrounding soft tissue contribute to the endogenous production of BMP2. In this study we used a mandibular canine segmental defect model (35 mm), periosteum was excised and also the delayed reconstruction group was included in this study in addition to the control group. We investigated the effect of different reconstruction settings on the quantity and quality of bony regenerates; on the production of endogenous BMP2 from the soft tissue bed of the defects and finally we tried to explore the source of this rhBMP2- induced endogenous BMP2 production both in vivo and in vitro. This study demonstrated that rhBMP2 delivery is more effective in immediate reconstruction of large mandibular segmental defects. Immediate delivery of rhBMP2 yielded more adequate reconstruction of the defect after 12 weeks, evident by the quantity and quality of the bone regenerate. Only in the immediate reconstruction group, the advantageous bone parameters were associated with significant up-regulation of BMP2 mRNA and protein in the soft tissue bed of the defect. This suggests that endogenous-BMP2 is important in maintaining the short-acting effect of the delivered rhBMP2. Regarding the source of the endogenous-BMP2, protein co-localization with ECs marker suggested that these cells could be the source for the endogenous BMP2 secretion in response to rhBMP2 treatment. This was confirmed by the in-vitro results on both the mRNA and protein levels. The gradual increase in expression of BMP2 mRNA and the significant upregulation of secreted BMP2 protein upon stimulation of human umbilical vein endothelial cells with 100-ng/ml rhBMP2 recognized a new mechanism of positive feed back response of ECs in response to BMP2 treatment.
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The Mechanisms of Fluoride Uptake by the Brush-Border Membrane Vesicles (BBMV) of Rabbit Small Intestine and KidneyIngested fluoride is absorbed rapidly from the gastrointestinal tract The literature indicates the following about the gastrointestinal absorption of fluoride: 1. the rate and extent of absorption are reduced by certain divalent and trivalent cations; 2 . the rate of absorption from the intact stomach is dependent on the magnitude of the transmucosal pH gradient; 3. the rate of absorption from the intact small intestine is not affected significantly by the pH of the bulk solution; 4. there is evidence that some unidentified, energy-requiring mechanism(s) may be involved in the intestinal absorption of fluoride; 5. although DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate) has little or no effect on fluoride movement across the human red blood cell membrane or the cortical collecting duct of the rabbit, it partially inhibits uptake by rat submandibular salivary cells. This study was carried out to test the hypothesis that the intestinal and renal absorption of fluoride occurs by more than one mechanism. That is, some fluoride is absorbed in a pH-dependent manner by HF diffusion through the apical membrane of intestinal cells, possibly via aquaporins. The bulk of fluoride, however, is absorbed as ionic fluoride via other routes possibly including passage through intercellular gap junctions, aquaporins, F'-C1‘ and/or F'-HCCV exchangers), conductive pathway and specific anion-transporting protein carriers. The specific aims of this study were to determine the effects of pH, pH gradients, sodium, potassium, chloride and bicarbonate gradients, DIDS ( a specific inhibitor of anion transport), bis-( 13-di butyl barbituric acid) pentamethine oxonol (diBAC, another specific inhibitor of anion transport), diethylpyrocarbonate (DEP, a histidine-specific reactive reagent), parachloromercuri-benzene sulfonate (PCMBS, a sulfhydryl-modifying reagent which is an inhibitor of aquaporins), and valinomycin on the movement of fluoride across brush border membrane vesicles (BBMV) prepared from the proximal intestinal mucosa and renal cortex of the rabbit The effect of pH gradients on fluoride transfer in everted intestinal sacs from the rat was also studied To accomplish the goals stated, two models were used: (1) the "everted sac" technique using tissue from rats; and (2) BBMV prepared from intestinal mucosal scrapings and renal cortex of rabbits. Both methods allow control of the compositions of the solutions on both surfaces. The everted sac technique involves the full thickness of the intestinal wall whereas BBMV involve only cell membranes from the luminal aspect of the mucosal cells (mainly enterocyte and some Goblet cells, enteroendocrine cells, Paneth cells, etc.). A comparison of the findings using these two approaches may show that the variables to be tested have different effects depending on the model and thus reveal the existence of different absorptive mechanisms or pathways. The variables to be tested included: (1) pH; (2) pH gradients; (3) specific inhibitors of (a) anion transport (DIDS and diBAC, which combine with the anion transporter to form a stable derivative to inhibit anion transport) and (b) proton transport (DEP, a histidinespecific reactive reagent which has been used to characterize proton and proton-coupled transport); (4) PCMBS, a sulfhydryl-modifying reagent which is a non-specific inhibitor of several transport systems including aquaporins; (5) valinomycin; and (6 ) gradients of sodium and potassium. The mechanism(s) involved in the absorption of fluoride from the intestinal tract remain poorly defined. The literature indicates that the rate of fluoride transport or migration across several types of epithelia and cell membranes is directly proportional to the magnitude of the pH gradient This dependency, however, appears not to apply to the intestinal epithelium. The present studies were designed to clarify this matter and thus contribute to an improved understanding of the basic mechanisms and pathways involved in the transport of fluoride in biological systems. The findings may have implications for the transport of other anions as well.
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Cellular and Immunocytochemical Response to Mandibular Distraction Using an Implanted Lengthening DeviceDistraction osteogenesis (DO) is a biologic process that generates new bone between surfaces of bone segments, which are gradually separated by traction forces. It is a uniquely effective method with multiple applications in the craniofacial region. This concept has been the basis of all bone-lengthening operations; it involved an osteotomy of the shortened bone and an external/internal fixator device, which slowly elongates the bone to its new dimension while a bony callus is being formed at the side to distraction. The biology of DO is similar to callus fracture healing. The bony regenerate passes through the same phases: formation of a collagen fibril template, mineralization, bony union and finally remodeling. The mechanisms by which the mechanical stresses applied to the bone tissue cause the cells to proliferate and form new bone are not well understood. More studies are needed to understand the cellular events underlying DO and the effects of the strains applied during DO on cellular proliferation and mineral apposition.
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Alterations in Articular Cartilage of the Rabbit Mandibular Condyle Following Surgical Induction of Anterior Disc Displacement: Light and Electron Microscopic Immunocytochemistry Using Colloidal Gold ConjugatesThe purpose of this study was to test the hypothesis that surgical induction of anterior disc displacement (ADD) in the rabbit craniomandibular joints (CMJ) will lead to degenerative osteoarthritic changes detectable a t the molecular, subcellular and cellular levels in the articular cartilage of the rabbit mandibular condyle. Ultrastructural features of the normal rabbit mandibular condyle were compared to those of experimental condyles a t two weeks following induction of ADD. The quantities of type-VI and -IX collagens, as well as the components of proteoglycans, such as chondroitin-4-sulfate (C4S), chondroitin-6-sulfate (C6S), k e ra tan sulfate (KS) and link protein (LP) were measured using immunogold labeling technique at the light and the electron microscopic levels. The right joint of each of 20 rabbits was exposed surgically, and all discal attachments were severed except for th e posterior attachment. The disc was then displaced anteriorly and sutured to the zygomatic arch. The left joint served as a sham -operated control. Ten additional joints were used as non operated controls. Deeply anesthetized rabbits were perfused with 2% buffered formalin two weeks after surgery. The mandibular condyles were excised and decalcified in ethylenediam inetetraacetic acid (EDTA). Paraffin embedded tissues were sectioned a t 5 (im for light microscopic study, while water-soluble plastic embedded sections were used for electron microscopy. Sections were incubated in monoclonal antibodies directed against C4S, C6S, KS and LP, and in polyclonal antibodies against type-VI and -IX collagens. After incubation in the appropriate colloidal gold conjugated secondary antibodies, tissue sections were studied with light and electron microscopes. In addition, immunostaining for proliferating cell nuclear antigen (PCNA) was performed using paraffin sections, and the PCNA indices of control and experimental condyles were determined. Pathological alterations were obvious in the experimental condyles, and appeared to be characteristic osteoarthritic changes. These include cartilage neovascularization, chondrocyte clustering, vacuolation, loss of extracellular matrix next to the membranes of chondrocytes, and an increase in num ber of apoptotic chondrocytes. Increased num bers of PCNA-positive cells in the osteoarthritic cartilage of the experimental group indicated a n active chondrocytic proliferation. Ultrastructural changes in injured chondrocytes included increased amounts of RER and Golgi, suggesting an increase in the synthesis and secretion of possibly degradative enzymes with a decrease in the normal secretory products. The results of th e immunocytochemistry using colloidal gold conjugates both a t the light and electron microscopic levels showed statistically significant depletion of C4S, C6S, KS, LP, type-VI collagen and type-IX collagen in the osteoarthritic cartilage (P < 0.05). The reduction of binding molecules such as LP, type-VI and type-IX collagens suggest a possible mechanism for the observed loss of integrity of the extracellular matrix. It is concluded that surgical induction of ADD in the rabbit CMJ leads to molecular, cellular and extracellular alterations in the articular cartilage of the mandibular condyle similar to those described previously in hum an ADD and in osteoarthritis of other synovial joints. The results of this study provide evidence that the loss of the shock absorber function of the disc, and the exposure of the condyles to overloading may cause the injured chondrocytes to secrete degenerative cytokines as indicated by the loss of proteoglycans, binding collagens and LP. These molecular changes are expressed a t the subcellular and cellular levels as osteoarthritis or degenerative joint disease.
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Recombinant Bone Morphogenetic Protein-2 Induces Up-Regulation of Angiogenesis and Inflammatory Transcripts: Role of Reactive Oxygen SpeciesLarge bone defects in the oral and maxillofacial region are mostly secondary to tumor resection, gunshot wounds or craniofacial anomalies. Reconstruction of large bone defects remains a clinical challenge despite the ability of bone to regenerate itself after fracture, mainly because bone regeneration requires recruitment of new cells as well as development of new bone tissue in order to restore anatomical and mechanical functions. Several biological and mechanical factors regulate bone formation. Early vascularization plays a critical role in skeletal bone development and bone fracture repair, and without a vascular supply, osteogenesis is impaired (Glowacki 1998; Akeno, Czyzyk-Krzeska et al. 2001; Carano and Filvaroff 2003). Furthermore, in the treatment of bone defects, vascularized bone grafts show less bone remodeling when compared to non-vascularized bone grafts (Cutting and McCarthy 1983; Wang, Yamazaki et al. 1996). This highlights the importance of angiogenesis in bone formation and remodeling. The close proximity of osteoblasts and osteoclasts to endothelial cells during bone formation suggests there is a cross-talk between these cells. Osteogenesis-inducing growth factors, such as bone morphogenetic proteins (BMPs), especially BMP-2 and -7, and vascular endothelial growth factor (VEGF) which is known to have a major role in angiogenesis, have been reported in many studies to play a major role in osteoblast-endothelial cell communication (Mayer, Bertram et al. 2005). The general goal of this study is to understand some of the molecular events that occur at the site of bone healing and the interaction of local growth factors produced by resident cells such as osteoprogenitor and endothelial cells. This will help us in developing techniques that enhance bone formation and provide better integration of bone grafts in the recipient site. Specifically, the aim of this study is to understand the mechanism by which recombinant bone morphogenetic protein-2 (rhBMP-2) induces bone formation and whether or not the effect of rhBMP-2 is through enhancing angiogenesis and inflammation.
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Porphyromonas gingivalis Escape-from Autophagy in Human Myeloid Dendritic Cells via Minor Mfa-1 Fimbra-DC-Sign InteractionsIn professional phagocytes, early receptor recognition is crucial to determine the fate of engulfed microorganisms. Among the many pattern recognition receptors (PRRs) expressed by dendritic cells (DCs), the C-type lectin DC-SIGN is of particular interest as it has been associated with immunosuppression by infecting pathogens. While autophagy has emerged as a major immune mechanism against microbes, very little is presently understood about its role in elimination o f intracellular pathogens; especially in the context o f the PRR diversity expressed by DCs. Hence, the study aimed to investigate the role of DC-SIGN targeting by the anaerobic pathogen Porphyromonas gingivalis in its intracellular survival within myeloid DCs and how intracellular routing through early and late endosomes, autophagosomes and lysosomes relate to this survival. Employed in this investigation were human monocyte derived DCs and a panel of isogenic fimbriae deficient mutant strains of P. gingivalis that express the DC-SIGN ligand (Mfa-1 fimbriae) and/or the TLR2 ligand (FimA fimbriae). The results show that uptake of P. gingivalis by the nonDC-SIGN dependent route resulted in intracellular killing and elimination of intracellular content of P. gingivalis. This route was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores. In contrast, DC-SIGN dependent uptake did not induce significant levels of Rab5, LC3- II, and LAMP1. Moreover, P. gingivalis was mostly contained within single membrane vesicles where it survived intracellularly. Survival was ameliorated by forced autophagy. These results suggest that myeloid DCs are fully capable of eliminating intracellular pathogens by autophagy but that selective engagement of DC-SIGN is a microbial tactic for evasion of antibacterial autophagy leading to intracellular survival.
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The Effect of Solvent Type and Content on Monomer Conversion of a Model Resin System and 5th Generation Dentin Bonding AgentsFifth generation dentin bonding agents contain a variety of solvents. These solvents have a range of evaporation rates, which leads to differing amounts of residual solvent remaining at time of cure. Residual solvent could affect resin polymerization, and thus resultant properties of the bonded resin/dentin interface.
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The Effect of Processing Techniques for rhBMP-2 Coated Titanium Implants on Alveolar Augmentation and Osseointegration in the Canine Supraalveolar Peri-Implant Defect ModelA current paradigm-shift in implant dentistry places restorative factors associated with esthetics and function in front of implant site selection based on bone quantity and quality. Marginal bone loss after implant placement, resorption of the edentulous alveolar ridge, bone defects from periodontal disease, and ridge aberrations due to trauma all challenge implant treatment driven by esthetics and function. Clinicians compensate for bone loss using bone augmentation procedures including bone grafts, bone materials, biologic mediators, barrier devices, or combinations thereof. The search for treatment modalities to address implant placement into compromised sites has lead to the development of a variety of products designed to replace or induce bone formation. Some believe an ideal material could be coated onto implants, to promote osseointegration, induce local bone formation, while not requiring adjunctive biomaterials, or procedures including placement of allogeneic and xenogeneic biomaterials, or autograft bone.
