The red, swollen, and painful gums and bone destruction due to periodontal disease could be effectively treated by beckoning the right kind of immune system cells to the inflamed tissues, according to a new pre-clinical study conducted by researchers at the University of Pittsburgh, including McGowan Institute for Regenerative Medicine faculty members Steven Little, PhD, associate professor and chair of the Department of Chemical and Petroleum Engineering, Pitt's Swanson School of Engineering, and Charles Sfeir, DDS, PhD, director, Center for Craniofacial Regeneration, and associate professor, Departments of Periodontics and Oral Biology, Pitt's School of Dental Medicine. Their findings, published in the early online version of the Proceedings of the National Academy of Sciences, may offer a new therapeutic paradigm for a condition that afflicts 78 million people in the U.S. alone.
Periodontal disease currently is treated by keeping oral bacteria in check with daily brushing and flossing as well as regular professional deep cleaning with scaling and root planing, which removes tartar above and below the gum line. In some hard-to-treat cases, antibiotics are given. These strategies of mechanical tartar removal and antimicrobial delivery aim to reduce the amount of oral bacteria on the tooth surface, explained co-author and co-investigator Dr. Sfeir.
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Authors: Andrew J. Glowacki, Sayuri Yoshizawa, Siddharth Jhunjhunwala, Andreia E. Vieira, Gustavo P. Garlet, Charles Sfeir, Steven R. Little
Title: Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes
Summary: The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu.
Source: Proc Natl Acad Sci USA. 2013 Nov 12;110(46):18525-30. Epub 2013 Oct 28.
PI: Fabrisia Ambrosio, PhD, PT and Aaron Barchowsky, PhD
Co Investigator: Donna Stolz, PhD
Title: Mechanisms of arsenic-induced muscle morbidity and reduced regenerative capacity
Project Description: Environmental toxicants, such as arsenic in drinking water, pose a significant risk for causing skeletal muscle myopathies, atrophy and reduced regenerative capacity; processes that are among the greatest factors contributing to declines in functional mobility and strong predictors of mortality. The negative impact of chronic exposure to arsenic on muscle metabolism and stem cell biology represents important pathogenic mechanisms for reducing the capacity to maintain, regenerate, and repair muscle. Advancing the mechanistic understanding of arsenic effects on muscle maintenance, stem cells, and healing capacity in the etiology of arsenic-induced muscle weakness and fatigue will aid in the design of strategies for improving outcomes in patients in arsenic endemic areas and increasing basic knowledge of mechanisms through which environmental exposures impair stem cell function.
Source: National Institute for Environmental Health and Safety: 1R01 ES023696-01
Term: 12/01/2013 – 11/30/2018
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