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Pathogenic role of peroxisome proliferator-activated receptor alpha in periodontitis

过氧化物酶体增殖物激活受体α在牙周炎中的致病作用

基本信息

批准号：
10363668
负责人：
Yang Hu
金额：
$ 19.9万
依托单位：
ADA FORSYTH INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-03 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10363668
关键词：
Address Adenoviruses Adult Affect Agonist Anti-Inflammatory Agents Antibiotics Antigens Antioxidants Autoimmune Diseases Bone Resorption Clinical Treatment Control Groups DNA Sequence Data Dental Plaque Deterioration Development Disease Dose Epithelial Cells Excision Fenofibrate Fibroblasts Foundations Future Gene Expression Genes Gingiva Goals Homeostasis Immune response Immunofluorescence Immunologic In Vitro Inflammation Inflammatory Injections Interleukin-1 Interleukin-10 Investigation Jaw Knock-out Knockout Mice Knowledge Lead Ligature Location Measures Mechanics Molecular Molecular Target Mouth Diseases Mus Nuclear Hormone Receptors Oral PPAR alpha PPAR gamma PPAR-beta Pathogenesis Pathogenicity Pathologic Pathology Pathway interactions Periodontal Diseases Periodontitis Periodontium Peroxisome Proliferator-Activated Receptors Peroxisome Proliferators Plant Roots Play Prevention Promoter Regions Public Health Quality of life RXR Regimen Regulation Research Response Elements Risk Role Splenocyte Stains System Systemic disease TNF gene Testing Therapeutic Time Tissues Toll-Like Receptor Pathway Tooth Diseases Tooth Loss Translating Wild Type Mouse angiogenesis antiangiogenesis therapy antimicrobial drug bone bone loss bone metabolism cell type conventional therapy cost cytokine economic cost experience in vivo lipid disorder lipid metabolism mRNA Expression microCT mouse model novel novel therapeutic intervention overexpression protein expression receptor binding receptor function targeted treatment transcription factor

项目摘要

Project Summary Periodontitis is an important public health problem among adults in the U.S., with major economic costs for prevention and treatment and significant impact on quality of life. Un-controlled periodontitis can cause ex- tensive tooth loss, jaw bone deterioration, and increased risk of developing systemic diseases. Conventional treatments that rely on antibiotics and mechanical removal of dental plaque are transiently effective because they indirectly address the inflammation and related immune responses that underlie periodontitis, but do not directly impact pathogenesis. Thus, there is a compelling need to investigate novel target molecules which di- rectly modulate pathogenesis for both inflammation and bone loss in periodontitis. It has been demonstrated that PPARα agonists (PPARαA), which is PPARα specific, have robust protective actions limiting inflammation in autoimmune disease, modulating inflammation. Our preliminary data suggest that a PPARαA, fenofibrate, has the potential to reduce periodontal inflammation and bone resorption in experimental periodontitis mouse mod- els, suggesting that the pathological role of PPARα in periodontitis deserves further investigation. We propose to test the hypothesis that PPARα not PPARβ or PPARγ plays important pathological roles in periodontitis. To that end, two distinct but complementary specific aims are proposed. Aim1 will determine that PPARα not PPARβ or PPARγ has expression level changes in periodontitis. Aim 2 will determine PPARα Knockout or overexpres- sion will affect inflammation and bone loss in experimental periodontitis mouse model. The understanding of expression level change of PPARα in periodontitis investigated during Aim1 will provide the foundation for Aim2. The goal is to reveal the role of PPARα in inflammatory regulation and in modulation of bone homeostasis during periodontal diseases. Building on previous experience and both Aim1 and Aim2 will lead to the development of novel, PPARα targeted therapies for periodontits and various other oral diseases. Successful completion of this project will lead to better understanding of the molecular and cellular role of PPARα in periodontitis, and translate this knowledge to develop an application system to achieve sustained release with noninvasive local delivery for the clinical treatment of periodontitis.

项目总结