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.

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Now showing 1 - 10 of 84
  • Publication
    Fibromodulin Reduces Scar Size and Increases Scar Tensile Strength in Normal and Excessive-Mechanical-Loading Porcine Cutaneous Wounds
    (2018-04-01) Jiang, Wenlu; Ting, Kang; Lee, Soonchul; Zara, Janette N.; Song, Richard; Li, Chenshuang; Chen, Eric; Zhang, Xinli; Zhao, Zhihe; Soo, Chia; Zheng, Zhong
    Hypertrophic scarring is a major postoperative complication which leads to severe disfigurement and dysfunction in patients and usually requires multiple surgical revisions due to its high recurrence rates. Excessive-mechanical-loading across wounds is an important initiator of hypertrophic scarring formation. In this study, we demonstrate that intradermal administration of a single extracellular matrix (ECM) molecule—fibromodulin (FMOD) protein—can significantly reduce scar size, increase tensile strength, and improve dermal collagen architecture organization in the normal and even excessive-mechanical-loading red Duroc pig wound models. Since pig skin is recognized by the Food and Drug Administration as the closest animal equivalent to human skin, and because red Duroc pigs show scarring that closely resembles human proliferative scarring and hypertrophic scarring, FMOD-based technologies hold high translational potential and applicability to human patients suffering from scarring—especially hypertrophic scarring. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
  • Publication
    Neural 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, Chia
    Arthritis, 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
  • Publication
    A 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 V
    Tissue 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.
  • Publication
    Cell-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, Songtao
    Patients 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.
  • Publication
    Non-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 D
    Non-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.
  • Publication
    Optical Diagnostics in the Oral Cavity: An Overview
    (2010-11-01) Wilder-Smith, P; Holtzman, J; Epstein, J; Le, A
    As the emphasis shifts from damage mitigation to disease prevention or reversal of early disease in the oral cavity, the need for sensitive and accurate detection and diagnostic tools become more important. Many novel and emergent optical diagnostic modalities for the oral cavity are becoming available to clinicians with a variety of desirable attributes including: (i) non-invasiveness, (ii) absence of ionizing radiation, (iii) patient-friendliness, (iv) real-time information (v) repeatability, and (vi) high-resolution surface and subsurface images. In this article, the principles behind optical diagnostic approaches, their feasibility and applicability for imaging soft and hard tissues, and their potential usefulness as a tool in the diagnosis of oral mucosal lesions, dental pathologies, and other dental applications will be reviewed. The clinical applications of light-based imaging technologies in the oral cavity and of their derivative devices will be discussed to provide the reader with a comprehensive understanding of emergent diagnostic modalities. © 2010 John Wiley & Sons A/S.
  • Publication
    Neural Progenitor-like Cells Induced from Human Gingiva-derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration
    (2017-02-01) Zhang, Qunzhou; Nguyen, Phuong; Xu, Qilin; Park, Wonse; Lee, Sunim; Furuhashi, Akihiro; Le, Anh D
    Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells. After crush injury, iNPCs, compared with GMSCs, displayed superior therapeutic effects on axonal regeneration at both the injury site and the distal segment of the injured sciatic nerve. Mechanistically, transplantation of GMSCs, especially iNPCs, significantly attenuated injury-triggered increase in the expression of c-Jun, a transcription factor that functions as a major negative regulator of myelination and plays a central role in dedifferentiation/reprogramming of Schwann cells into a progenitor-like state. Meanwhile, our results also demonstrate that transplantation of GMSCs and iNPCs consistently increased the expression of Krox-20/EGR2, a transcription factor that governs the expression of myelin proteins and facilitates myelination. Altogether, our findings suggest that transplantation of GMSCs and iNPCs promotes peripheral nerve repair/regeneration, possibly by promoting remyelination of Schwann cells mediated via the regulation of the antagonistic myelination regulators, c-Jun and Krox-20/EGR2. © AlphaMed Press, 2016 The Authors.
  • Publication
    Evoked and Spontaneous Pain Assessment During Tooth Pulp Injury
    (2020-12-01) Rossi, Heather Lynn; See, Lily Pachanin; Foster, William; Pitake, Saumitra; Gibbs, Jennifer; Schmidt, Brian; Mitchell, Claire H.; Abdus-Saboor, Ishmail
    Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain. © 2020, The Author(s).
  • Publication
    A Simple Technique Using a Modified Nance Appliance as Anchorage for Maxillary Molar Distalization—Two Case Reports
    (2022-01-02) Li, Chenshuang; Chung, Chun-Hsi
    Maxillary molar distalization to correct a dental Class II molar relationship and to create space to relieve crowding has been a long-lasting subject of debate in orthodontics. Generally, to distalize maxillary molars, an intra-arch distalization appliance is favored over an inter-arch appliance since it does not utilize mandibular dentition as an anchorage, so some unwanted side effects on mandibular incisors can be avoided. A variety of intra-arch appliances have been developed to distalize maxillary molars, such as the pendulum, Jones jig, first class appliance, distal jet, and modified C-palatal plate. Although they could achieve efficient molar distalization, the learning curve of proper appliance insertion and activation is relatively long. In addition, the appliances are not comfortable for the patients due to the bulky activation units, especially when the activation units are designed in the palatal area. The current manuscript describes a novel and effective maxillary intra-arch molar distalization appliance—a modified Nance appliance technique, which consists of: (1) palatally, a big acrylic button against the palatal rugae and connected to the premolars with wide mesh pads; (2) buccally, regular brackets on maxillary premolars and first molars with sectional round stainless steel archwires and open coil springs between the second premolar and first molar. Either bilateral or unilateral maxillary molar distalization can be achieved with this appliance, and the Class II elastics are not needed. It is simple to be fabricated, delivered, and activated, and it is comfortable for patients. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.