Mechanisms of Resolvin E1 in Periodontal Regeneration

Resolvin E1 在牙周再生中的作用机制

• 批准号: 8861681
• 负责人: THOMAS Elliott VAN DYKE
• 金额: $ 49.53万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8861681
• 关键词: Acute; Address; Adult; Agonist; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Binding; Biochemistry; Biological Factors; Biomedical Engineering; Bone Regeneration; Cell physiology; Cellular biology; Chronic; Data; Defect; Development; Disease; Failure; Goals; Homeostasis; Immunosuppression; Inflammation; Inflammatory; Knock-out; Knowledge; Lesion; Link; Lipoxins; Literature; Mediating; Mediator of activation protein; Molecular; Mus; Myeloid Cells; National Institute of Dental and Craniofacial Research; Natural regeneration; Operative Surgical Procedures; Oral; Osteoblasts; Osteoclasts; Osteogenesis; Outcome; Pathology; Pathway interactions; Periodontal Diseases; Periodontitis; Population; Positioning Attribute; Postoperative Period; Procedures; Process; Public Health; Publishing; Reporting; Research; Resolution; Role; Serum; Signal Pathway; Signal Transduction; System; Techniques; Tissue Engineering; Tissues; Topical application; Transgenic Mice; United States; Work; Wound Healing; base; bone cell; craniofacial; experience; inhibitor/antagonist; injured; lipid mediator; neutrophil; novel; novel therapeutics; pre-clinical; programs; public health relevance; receptor; reconstruction; regenerative therapy; research study; response; soft tissue; success; tissue reconstruction; tissue regeneration

 DESCRIPTION (provided by applicant): Control of inflammation in periodontal regeneration is a major public health problem. Approximately 50% of the population of the United States has some form of periodontal disease and tissue engineering procedures cannot completely restore hard and soft tissues. Control of endogenous inflammation is an absolute requirement for tissue engineering success. There is a critical need for new therapeutics in regeneration that control local inflammation. The long-term goal of this R01 proposal is to utilize natural resolution of inflammation to control local inflammation and accelerate regeneration. Resolvins mediate resolution of inflammation facilitating periodontal regeneration and a return to homeostasis. Our group introduced the novel concept that inflammatory disease may result from a failure of active resolution. Accumulating evidence suggests that agonists of endogenous resolution programs may be the best approach to control inflammation in periodontal regeneration and reconstruction. The Central Hypothesis is that resolution of inflammation pathways and mediators can be harnessed to control inflammation in periodontal tissues enabling regeneration and reconstruction. We have demonstrated that delivery of lipoxins and resolvins greatly enhances tissue regeneration by control of inflammation. Resolvins also have actions beyond control of neutrophils including receptor mediated control of osteoclast and osteoblast function in wound healing and bone regeneration. We will identify key endogenous control mechanisms for bone formation induced by RvE1 using specific RvE1 receptor knock-out (KO) and receptor over-expressing transgenic mice, determine the basis for bone cell responses to RvE1 by elucidation of signal anabolic pathways that promote osteoblast mediated bone formation and limit osteoclast activity, and unravel the complexities of lipid mediator synergy and characterize hetero- specific resolution agonist amplification by determining pro and anti-inflammatory lipid mediator profiles induced by RvE1. Results from these studies will advance our knowledge of mechanisms in natural resolution of inflammation in tissue regeneration to develop novel bioengineering-based strategies targeted for periodontal regeneration. Our experienced research team consists of experts in cell biology, pharmacological biochemistry, animal models and periodontal regeneration that are well positioned to carry out this project.

 描述（由适用提供）：牙周再生中炎症的控制是一个主要的公共卫生问题。美国约有50％的人口具有某种形式的牙周疾病，组织工程程序无法完全恢复硬和柔软的时机。控制内源性炎症是组织工程成功的绝对要求。在控制局部炎症的再生中，需要新的治疗。该R01提案的长期目标是利用自然解决炎症来控制局部炎症和加速再生。解决炎症的中位分辨率促进了牙周再生和回归体内平衡。我们的小组介绍了一个新的概念，即炎症性疾病可能是由于主动解决的失败而导致的。积累的证据表明，内源分辨率计划的激动剂可能是控制牙周再生和重建中炎症的最佳方法。中心假设是，可以利用炎症途径和介体的分辨率来控制牙周组织中的注射，从而能够再生和重建。我们已经证明，通过控制炎症，脂蛋白和溶解剂的递送大大增强了组织再生。 Resolvins还具有无法控制的中性粒细胞的作用，包括受体介导的破骨细胞和成骨细胞功能在伤口愈合和骨骼再生中的控制。 We will identify key endogenous control mechanisms for bone formation induced by RvE1 using specific RvE1 receptor knock-out (KO) and receptor over-expressing transgenic mice, determine the basis for bone cell responses to RvE1 by elucidation of signal anabolic pathways that promote osteoblast mediated bone formation and limit osteoclast activity, and unravel the complexities of lipid mediator synergy and characterize hetero- specific通过确定由RVE1诱导的Pro和抗炎脂质介质轮廓来分辨激动剂放大。这些研究的结果将提高我们对组织再生中炎症自然炎症的机制的了解，以开发针对牙周再生的新型基于生物工程的策略。我们经验丰富的研究团队由细胞生物学，药物生物化学，动物模型和牙周再生方面的专家组成，这些专家有能力执行该项目。