Penn Dental Medicine
Established in 1878, Penn Dental Medicine is among the oldest university-affiliated dental schools in the nation. The school's mission is to transform global oral health and well-being through exceptional clinical care, innovation, education, and research.
PublicationMesenchymal Stem Cells Derived From Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis (Journal of Immunology (2009) 183, (7787-7798))(2010-02-01) Zhang, Qunzhou; Shi, Hong; Liu, Yi; Uyanne, Jettie; Shi, Yufang; Shi, Songtao; Le, Anh D PublicationEpigenetic Changes in the Innate Response of Gingival Epithelium(2014-05-28) Abdolhosseini, MahsaIn this study we showed TLR2 CpG promoter methylation in periodontitis affected human gingival tissues and in primary human gingival epithelial cells chronically stimulated with P. gingivalis that may instigate epithelial dysbiosis that may create a unique pathogen niche in the gingival crevice and susceptibility to periodontitis. PublicationNeural EGFL Like 1 as a Potential Pro-Chondrogenic, Anti-Inflammatory Dual-Functional Disease-Modifying Osteoarthritis Drug(2020-01-01) Li, Chenshuang; Zheng, Zhong; Ha, Pin; Jiang, Wenlu; Berthiaume, Emily A.; Lee, Seungjun; Mills, Zane; Pan, Hsinchuan; Chen, Eric C.; Jiang, Jie; Culiat, Cymbaline T.; Zhang, Xinli; Ting, Kang; Soo, ChiaArthritis, an inflammatory condition that causes pain and cartilage destruction in joints, affects over 54.4 million people in the US alone. Here, for the first time, we demonstrated the emerging role of neural EGFL like 1 (NELL-1) in arthritis pathogenesis by showing that Nell-1-haploinsufficient (Nell-1+/6R) mice had accelerated and aggravated osteoarthritis (OA) progression with elevated inflammatory markers in both spontaneous primary OA and chemical-induced secondary OA models. In the chemical-induced OA model, intra-articular injection of interleukin (IL)1β induced more severe inflammation and cartilage degradation in the knee joints of Nell-1+/6R mice than in wildtype animals. Mechanistically, in addition to its pro-chondrogenic potency, NELL-1 also effectively suppressed the expression of inflammatory cytokines and their downstream cartilage catabolic enzymes by upregulating runt-related transcription factor (RUNX)1 in mouse and human articular cartilage chondrocytes. Notably, NELL-1 significantly reduced IL1β-stimulated inflammation and damage to articular cartilage in vivo. In particular, NELL-1 administration markedly reduced the symptoms of antalgic gait observed in IL1β-challenged Nell-1+/6R mice. Therefore, NELL-1 is a promising pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug (DMOAD) candidate for preventing and suppressing arthritis-related cartilage damage. © 2019 Elsevier Ltd PublicationA Novel 3-Dimensional Culture System as an In Vitro Model for Studying Oral Cancer Cell Invasion(2005-12-01) Duong, Hai S; Le, Anh D; Zhang, Qunzhou; Messadi, Diana VTissue microenvironment plays a critical role in tumour growth and invasion. This study established a novel 3-dimensional (3-D) cell invasion model for direct microscopic observation of oral cancer cell invasion into the underlying basement membrane and connective tissue stroma. A multilayer cell construct was developed using the OptiCell chamber, consisting of a lower layer of oral mucosa fibroblasts embedded in collagen gel and an overlaying upper layer of oral cancer cells. The two layers are separated by a basement membrane composed of reconstituted extracellular matrix. To verify the applicability of the cell invasion model, multilayer cell constructs of oral squamous cell carcinoma and oral mucosal fibroblasts were exposed to extrinsic urokinase-type plasminogen activator (uPA) or plasminogen activator inhibitor (PAI-1), which are known effectors of cell migration. In addition, the constructs were exposed to both normoxic and hypoxic culture conditions. Microscopic study showed that the presence of uPA enhanced cell invasion, while PAI-1 inhibited cell migration. Western blot and zymographic analysis demonstrated that hypoxia up-regulated uPA and matrix metalloproteinases (MMPs) expression and activity; conversely, PAI-1 level was down-regulated in response to hypoxic challenge as compared to normoxic condition. Our results indicated that the novel 3-D invasion model could serve as an excellent in vitro model to study cancer cell invasion and to test conditions or mediators of cellular migration. © 2005 Blackwell Publishing Ltd. PublicationCell-based Immunotherapy with Mesenchymal Stem Cells Cures Bisphosphonate-related Osteonecrosis of the Jaw-like Disease in Mice(2010-07-01) Kikuiri, Takashi; Kim, Insoo; Yamaza, Takyoshi; Akiyama, Kentaro; Zhang, Qunzhou; Li, Yunsheng; Chen, Chider; Chen, Wanjun; Wang, Songlin; Le, Anh D; Shi, SongtaoPatients on high-dose bisphosphonate and immunosuppressive therapy have an increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ); despite the disease severity, its pathophysiology remains unknown, and appropriate therapy is not established. Here we have developed a mouse model of BRONJ-like disease that recapitulates major clinical and radiographic manifestations of the human disease, including characteristic features of an open alveolar socket, exposed necrotic bone or sequestra, increased inflammatory infiltrates, osseous sclerosis, and radiopaque alveolar bone. We show that administration of zoledronate, a potent aminobisphosphonate, and dexamethasone, an immunosuppressant drug, causes BRONJ-like disease in mice in part by suppressing the adaptive regulatory T cells, Tregs, and activating the inflammatory T-helper-producing interleukin 17 cells, Th17. Most interestingly, we demonstrate that systemic infusion with mesenchymal stem cells (MSCs) prevents and cures BRONJ-like disease possibly via induction of peripheral tolerance, shown as an inhibition of Th17 and increase in Treg cells. The suppressed Tregs/Th17 ratio in zoledronate- and dexamethasone-treated mice is restored in mice undergoing salvage therapy with Tregs. These findings provide evidence of an immunity-based mechanism of BRONJ-like disease and support the rationale for in vivo immunomodulatory therapy using Tregs or MSCs to treat BRONJ. © 2010 American Society for Bone and Mineral Research. PublicationGingival MSCs Improve Bone Phenotype in Ovariectomy-Induced Osteoporosis via Programmed Cell Death Pathway(2019-12-19) Alghaithi, SultanEstrogen deficiency-related osteoporosis is a skeletal system disorder that affects women after menopause taking a toll on financial and health institutions. Gingival Mesenchymal Stem cells (GMSCs) are a distinctive population of dental tissue-derived stem cells that possess uniquely high proliferation abilities and are capable of self-maintenance and multipotent differentiation. Their use has been investigated in different disease model applications, including cutaneous wound healing models, colitis, and allergy-related inflammatory disease models, but their effect on the bone phenotype of ovariectomy-induced osteoporosis hasn’t been explored. In our study, we show that a single systemic infusion of GMSCs elevated the bone mass reduction caused by Ovariectomy (OVX)-induced osteoporosis in both the femurs and mandibles of OVX mice, they also successfully rescued the function of the defective endogenous population of Bone Marrow Mesenchymal Stem Cells (BMMSCs). We saw that the systemic infusion of GMSCs exerted an immunomodulatory effect on the host, leading to the elevation of T-regulatory lymphocytes (T-regs) and the downregulation of T helper type 1 lymphocytes (Th1) levels in recipient OVX mice. Mechanistically, PD-1/PD-L1 is a popular cellular death pathway being heavily investigated in multiple research fields, In our study, we found that GMSC expresses PD-L1 and that the improved bone phenotype resulting from the GMSC infusion was via the programmed cell death (PD-1/PD-L1) pathway triggering activated T-cell apoptosis in the OVX mice, eventually resulting in an improvement of the bone phenotype. PublicationNon-exposed Bisphosphonate-related Osteonecrosis of the Jaw: A Critical Assessment of Current Definition, Staging, and Treatment Guidelines(2012-10-01) Patel, S; Choyee, S; Uyanne, J; Nguyen, A L; Lee, P; Sedghizadeh, P P; Kumar, S K S; Lytle, J; Shi, S; Le, A DNon-exposed bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a newly reported complication arising from bisphosphonate therapy that presents with atypical symptoms and no apparent mucosal fenestration or exposure of necrotic bone. The clinical observation of the presence of necrotic bone underneath normal epithelial coverage was not conclusive for the diagnosis of BRONJ based on current guidelines established by the American Association of Oral and Maxillofacial Surgeons (AAOMS) and the American Society for Bone and Mineral Research (ASBMR), which specify the presence of clinically exposed necrotic bone for more than 8weeks. Hence, the purpose of this review is to critically assess the current guidelines for diagnosis and management of BRONJ and propose a modified staging system and treatment guidelines to properly address the non-exposed variant of BRONJ lesions. © 2012 John Wiley & Sons A/S. PublicationThe Change of Alveolar Bone Thickness on Mandibular Central Incisors of Skeletal Class II Patients After Orthodontic Treatment Using Cone-Beam Computed Tomography.(2019-05-17) Matsumoto, Kensuke; Sherrill-Mix, Scott; Boucher, Normand; Tanna, NipulObjective: To test the null hypothesis that orthodontic tooth movement does not create dehiscences and the sagittal width dimension of alveolar bone is maintained. Materials and Methods: In 60 skeletal class II patients, CBCT images at pre- (T1) and post-orthodontic treatment (T2) were obtained and the presence of dehiscences was recorded. Based on the presence of dehiscences at T1 and T2, the patients were divided into four groups. The alveolar bone thickness at the level of 2 (CEJ2), 5 (CEJ5), 10 (CEJ10), and 15 (CEJ15) mm from the cementoenamel junction (CEJ) was measured on CBCT images in cross section along the long axis on the central incisors. CBCT-synthesized lateral cephalometric images were analyzed. Statistical analysis and the Pearson correlation analyses were utilized at a pResults: CBCT imaging showed that 27.1% of the mandibular central incisors had dehiscences at T1. With pre-existing dehiscence, the incidence of dehiscence increased to 50% at T2. Patients that developed dehiscences after orthodontic treatment showed the highest percentage of alveolar bone loss (-23.7% at CEJ2, -19.9% at CEJ5 at T2). In the group where patients developed dehiscences after orthodontic treatment, there was statistically significant mean increase of L1-NB (3.1mm) and IMPA (9.8°) (pConclusions: When camouflaging skeletal Class II patients, the limits of mandibular anterior incisor forward movement might be less than previously thought. In order to prevent the development of inadvertent dehiscences during the orthodontic treatment, careful diagnosis with CBCT images is recommended. Furthermore, when excessive protrusion and/or proclination is planned, additional treatment modalities such as orthognathic surgery, tooth extraction, and partial corticotomy with bone grafting should be considered. PublicationExperimental Study on the Acellular Demal Matrix Graft for the Root Coverage in Dog(2006-03-01) Cho, Min-Young; Lee, Seoung-Ho; Han, Keum-Ah; Lee, Jun-Young; Jeon, Hyeran H; Kang, Na-Ra; Kim, Myung-RaeMucogingival surgery is a plastic surgical procedure designed to correct defects in the morphology, position, and dimensions of the gingiva surrounding the teeth. Many surgical techniques have been reported in mucogingival surgery. Since these procedures also include the soft tissue esthetic approach, the term "periodontal plastic surgery" has been proposed to be more appropriate.1 Root coverage is a procedure that falls with this definition, and it has attracted more interest than others. PublicationHuman Oral Mucosa and Gingiva: A Unique Reservoir for Mesenchymal Stem Cells(2012-11-01) Zhang, Q Z; Nguyen, A L; Yu, W H; Le, A DMesenchymal stem cells (MSCs) represent a heterogeneous population of progenitor cells with self-renewal and multipotent differentiation potential. Aside from their regenerative role, extensive in vitro and in vivo studies have demonstrated that MSCs are capable of potent immunomodulatory effects on a variety of innate and adaptive immune cells. In this article, we will review recent experimental studies on the characterization of a unique population of MSCs derived from human oral mucosa and gingiva, especially their immunomodulatory and anti-inflammatory functions and their application in the treatment of several in vivo models of inflammatory diseases. The ease of isolation, accessible tissue source, and rapid ex vivo expansion, with maintenance of stable stem-cell-like phenotypes, render oral mucosa- and gingiva-derived MSCs a promising alternative cell source for MSC-based therapies. © 2012 International & American Associations for Dental Research.