This collection contains theses and dissertations submitted by graduate students under the Department of Oral Biology for either a Master of Science degree or a Doctor of Philosophy degree.

Recent Submissions

  • The Effect of Nrf2 on Inflammatory Responses of Human Monocytic Cells After Blue Light Exposure

    Trotter, Leigh Ann; Trotter, Leigh Ann; Department of Oral Biology (12-Apr)
    Blue light treatment alters cellular signaling and affects intracellular biochemical processes in tissues. PURPOSE: This study determined the ability of blue light to modulate Nrf2 and decrease LPS-induced secretion of pro-inflammatory cytokines from cultured, human monocytic cells. METHODS: Cultured THP-1 human monocytic cells were exposed to LPS and blue light treatment. Western Blot analyses, EMSA, and ELISA were used to evaluate NF?B, Nrf2, HO-1, TNF-?, IL-6 and IL-8 production. RESULTS: Light treatment increased nuclear Nrf2 and increased HO-1. Cells pretreated with light had no detectable NF?B-DNA binding. LPS treatment increased nuclear NF?B, and had little effect on Nrf2. Light pre-treatment significantly decreased the amount of TNF-? by 63% and IL-8 by 55%. CONCLUSIONS: Blue light increases the production of Nrf2 and HO-1, decreases the ability of Nf?B to bind in the nucleus, and leads to a decrease in the secretion of pro-inflammatory proteins in human monocytic cells.
  • The role of Toll-like receptor (TLR) 2 in the systemic immune response profile of mice induced to develop squamous cell carcinoma of the upper aerodigestive tract

    El-Shafey, Sally; El-Shafey, Sally; Department of Oral Biology (4/1/2017)
    Background Head and necksquamous cell carcinomais associated with immunosuppression, a state in which the progression of cancer is associated with disturbances in the immune system functions. Emerging studies suggest a fundamental role for the innate immune system, particularly Toll-like receptor 2 (TLR2), in this process.QuestionsIn this study, we investigated the potential roles of TLR2 on systemic immune profile in a mouse model of headand necksquamous cell carcinoma.MethodsTwo different protocols of a mouse model of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis to induce head and neck squamous cell carcinoma were used. To evaluate the systemic immune profiles, total RNA wasisolated from the spleens of four groups of animals, including carcinogen-treated and control untreated wild-type and toll-like receptor 2-deficient animals. Quantitative real-time PCR was performed forgenesrepresentative of house-keeping genes, type 1 and type 2 immune responses, regulatory T and B cells, and adenosine receptors.Results and ConclusionIn the standard protocol of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis, there was asignificant upregulation of adenosine receptor A2a in the spleens of wild type iiimice treatedwith4-nitroquinoline 1-oxide and ethanolrelative to wild type untreatedanimals. In the standard protocol of carcinogenesis, there was a significant upregulation of CD39 in the spleens of TLR2-koanimalstreated with 4-nitroquinoline 1-oxide and ethanol relative to untreated TLR2-ko mice. These results suggest that carcinogenesis in the upper aerodigestive tract is associated with alterations in the systemic immune profile reflected in the spleen. However, the specific impact on the immune profiles appears to be affected by the presence or absence of TLR2.
  • SUSTAINED RELEASE FORMULATION FOR VASCULAR ENDOTHELIAL GROWTH FACTOR

    Elzinga, Jennifer Lynn; Department of Oral Biology (2/1/2013)
  • EFFECT OF MATRIX-BOUND BISPHOSPHONATES ON MONOCYTE DIFFERENTIATION AND OSTEOCLAST FUNCTION

    Abraham, Pheba; Abraham, Pheba; Department of Oral Biology (5/1/2017)
    This study was to explore the effect of local, matrix-bound bisphosphonates to monocytedifferentiation and osteoclast function in vitro. Experiments were designed using osteoassay plates. Cell-viability, differentiation, resorption pits and gene expression were analyzed to see the effect of matrix-bound BPs on monocyte differentiation and osteoclast function. EDTA was used as a chelating agent to remove the bound BPs. There was a dose dependent response in the differentiation and resorption pits. With chelation, there was increase in differentiation, resorption pits and increase in the calcium and PYD in the supernatant. Thus, matrix-bound Bisphosphonatesare biologically active and they inhibit monocyte differentiation and osteoclast function. Thereby removal of this matrix-bound drug can rescue osteoclast differentiation and function.
  • Inherent Gene Expression and Protein Profile Differences Between Alveolar and Basal Bone

    Alotaibi, Fawwaz; Alotaibi, Fawwaz; Department of Oral Biology (5/1/2015)
    The mandible is composed to two bone types: alveolar and basal. Previous studies on the mandible have shown that the alveolar bone resorbs more than the basal bone after tooth extraction or as a result of tooth movement. Reasons for why the resorption rates are different is not well understood. This research begins exploring the differences of the alveolar and basal bone by using comparison characteristics such as bone mineral density (BMD), gene expression, protein profiles, and number of osteocytes. The research investigates these characteristics by using Real time RCR to study the differences in gene expression and protein profiles of the alveolar and basal bone. Micro-CT was used in comparing density and bone architecture characteristics of the alveolar and basal bone. Immunohistochemistry was used to better understand how osteocytes are different between the two bone types in hopes of later being able to understand the differences in resorption rates. The real time PCR showed that four genes are expressed significantly higher in basal bone than alveolar bone: SOST, E-11, DMP-1, MEPE. Three of which are associated with mature osteocytes indicating that basal bone has more mature osteocyte phenotypes. Micro-CT data indicated that the basal bone is denser and less porous than alveolar bone. There was no significant difference in immunohistochemistry and further quantitative testing is needed to draw and significant correlation.
  • Effects of vitamin D supplementation on untreated chronic periodontitis

    Mogrovejo, Fernando; Master of Oral Biology (2016)
  • 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)

    Capetillo, Joseph F.; Department of Oral Biology (4/15/2016)
    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]
  • Changes in the RANK/RANKL/OPG Signaling System as a Mechanism of Zoledronate-Induced Osteonecrosis of the Jaw

    Lane, Jonathan; Department of Oral Biology (3/22/2016)
    Bisphosphonates (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.
  • Effect of an Er,Cr:YSGG Laser on P. Gingivalis-Contaminated Titanium Alloy Dental Implant Surfaces In Vitro

    Strever, Jason; Department of Oral Biology (2016-04)
    Implant 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.
  • Plasma Membrane Disruption in Orthodontic Tooth Movement

    Orellana, Maria F.; Department of Oral Biology (2002-04)
    (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.
  • Primary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogs

    Hussein, Khaled A.; Department of Oral Biology (2012-12)
    Very 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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