A Long Noncoding RNA Amerliorates Periodontitis via Distinct Epigenetic Pathways
长非编码 RNA 通过独特的表观遗传途径改善牙周炎
基本信息
- 批准号:10308042
- 负责人:
- 金额:$ 69.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-01 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:AdenovirusesAdultAgeAmericanAntigen-Antibody ComplexAtherosclerosisBinding ProteinsBiologicalBiological ProcessBiologyBloodBone MarrowBone Marrow Stem CellBone RegenerationBone ResorptionBone TissueCardiovascular systemCell Differentiation processCell ProliferationCellsClinicalClinical TrialsCodeCoinDental ClinicsDeteriorationDevelopmentDiabetes MellitusDiseaseDisease ProgressionElementsEndocrine systemEpigenetic ProcessEtiologyFDA approvedFamilyFoundationsFunctional disorderGene ClusterGene ExpressionGenesHuman GenomeImpairmentInflammationInflammatoryKnockout MiceLaboratoriesLengthLinkLiteratureMAP Kinase GeneMalignant NeoplasmsMeasurementMeasuresMetabolicModelingMolecularMolecular BiologyMusNeuraxisNucleotidesOral PathologyOsteoblastsOsteoclastsOsteogenesisOutcome StudyOutcomes ResearchPathogenesisPathologicPathologyPathway interactionsPatternPeriodontal DiseasesPeriodontitisPharmacologyPlayPreventiveProcessRNARNA BindingReproductive systemResearchResearch PersonnelResearch Project GrantsRoleSamplingSignal PathwayStromal CellsTLR4 geneTechniquesTherapeuticTherapeutic AgentsTherapeutic EffectTooth DiseasesTooth LossTranscriptUntranslated RNAUp-Regulationadult stem cellalveolar bonebasebonecell typegain of functiongene therapygenetic risk factorhuman diseaseinduced pluripotent stem cellinsightknockout genemacrophagemicroCTmicrobiome analysismouse modelnew therapeutic targetnext generationnovelnovel therapeuticsosteoclastogenesisosteogenicoverexpressionpalliativerelating to nervous systemside effectskillsstem cell differentiationtherapeutic evaluationtherapeutic targettherapeutically effectivetranscription factortranscriptome sequencingtranslational studyvirtual
项目摘要
Nearly 50% of American adults over age 30 have periodontal disease (PD). The basic pathology of PD
is excessive alveolar bone resorption leading to tooth loss. Furthermore, PD can trigger general inflammation,
adversely influencing cardiovascular, central nervous, reproductive and endocrine systems. Our laboratory has
explored a variety of strategies for treating this disease and is still actively searching for a more effective and
practical therapy with minimal side effects to cure the disease. Long noncoding RNAs (lncRNAs) are a family of
non-protein-coding transcripts with the length longer than 200 nucleotides. LncRNAs participate in a wide
repertoire of biological processes and play important roles in gene expression and posttranscriptional processes
and are also implicated in the pathogenesis of many diseases. However, the functions of lncRNAs in dental
diseases are just beginning to be uncovered. LncRNA ANRIL was the first shared genetic risk factor of
atherosclerosis, PD, diabetes and cancers, thereby coined to APCD. Our laboratory has performed extensive
preliminary studies including studies on lncRNA-APDC knockout mice. Our hypothesis is that lncR-APDC
inhibits inflammation, osteoclastic bone resorption and promotes osteogenesis and alveolar bone regeneration
through specific epigenetic pathways, by which efficiently targeting the pathophysiology of periodontitis. Aim 1
will determine the functions of lncR-APDC in periodontitis via loss- and gain-of-function approaches. Next
generation RNA-Seq will be performed to elucidate the expression patterns of the participating genes and cellular
pathways altered by the lncRNA dysregulation. Aim 2 will use state-of-the-art techniques to determine the
cellular localization of lncR-APDC and decipher the mechanisms by characterizing the protein and RNA binding
partners and chromosomal regions regulated by the lncR-APDC. Aim 3 will test the therapeutic effects of lncR-
APDC in periodontitis to determine lncR-APDC’s effect on inflammation, osteoclastic bone resorption and
alveolar bone regeneration. The results will provide a paradigm shift and advance the research field vertically in
three ways. Firstly, we have initially found that lncR-APDC could play a pivotal role in cell differentiation and
proliferation in PD. However, how this lncRNA is involved in PD progression is virtually unknown. Therefore, the
results will reveal a novel pathological mechanism of PD deterioration and progression. Secondly, we will
decipher the pathways of lncR-APDC modulating gene clusters in different cells playing active roles in the
periodontal microenvironment and their roles in the PD progression, which will lead to the discovery of novel
therapeutic targets. Finally, we will examine the potential utility of our newly constructed adenovirus conjugated
lncR-APDC, as a safe and effective therapeutic measure for PD in dental clinics. An interdisciplinary team of
investigators with complementary and synergistic skills will conduct the studies (Jake Chen – Experimental Oral
Pathology and Bone Biology; Qisheng Tu – Cell and Molecular Biology; Thomas Van Dyke – Periodontology
and RNA-Sequencing; Hans Johansson – RNA Biology and lncRNA FISH).
近50%的30岁以上的美国成年人患有牙周病(PD)。帕金森病的基本病理
过度的牙槽骨吸收导致牙齿脱落。此外,PD可引发全身炎症,
对心血管、中枢神经、生殖和内分泌系统产生不利影响。本实验室
探索了治疗这种疾病的各种策略,并仍在积极寻找更有效,
以最小的副作用来治愈疾病的实用疗法。长链非编码RNA(lncRNA)是一类
长度超过200个核苷酸的非蛋白质编码转录物。lncRNA参与了广泛的
在基因表达和转录后过程中发挥重要作用
并且还涉及许多疾病的发病机理。然而,lncRNA在牙本质中的功能,
疾病才刚刚开始被发现。LncRNA ANRIL是第一个共享的遗传风险因素,
动脉粥样硬化、PD、糖尿病和癌症,因此被称为APCD。我们的实验室进行了广泛的
初步研究,包括对lncRNA-APDC敲除小鼠的研究。我们假设lncR-APDC
抑制炎症、骨吸收、促进骨生成和牙槽骨再生
通过特定的表观遗传途径,有效地靶向牙周炎的病理生理学。要求1
将通过功能丧失和获得方法确定lncR-APDC在牙周炎中的功能。下
将进行第二代RNA-Seq以阐明参与基因和细胞的表达模式。
通过lncRNA失调改变的途径。目标2将使用最先进的技术来确定
lncR-APDC的细胞定位,并通过表征蛋白质和RNA结合来破译机制
由lncR-APDC调控的伴侣和染色体区域。目的3将测试lncR的治疗效果-
牙周炎中的APDC,以确定lncR-APDC对炎症、骨质疏松性骨吸收和
牙槽骨再生研究结果将提供一种范式转变,并在垂直方向上推进研究领域。
三种方式。首先,我们初步发现lncR-APDC在细胞分化中起关键作用,
在PD中增殖。然而,这种lncRNA如何参与PD进展几乎是未知的。因此
结果将揭示PD恶化和进展的新病理机制。其次,我们将
破译不同细胞中lncR-APDC调节基因簇在细胞凋亡中发挥积极作用的途径,
牙周微环境及其在PD进展中的作用,这将导致发现新的
治疗目标最后,我们将研究我们新构建的腺病毒结合的潜在效用,
lncR-APDC是一种安全有效的治疗PD的方法。的跨学科团队
具有互补和协同技能的研究人员将进行研究(Jake Chen-实验口语
病理学和骨生物学; Qisheng Tu-细胞和分子生物学;托马斯货车Dyke-牙周病学
和RNA测序; Hans Johansson-RNA Biology and lncRNA FISH)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JAKE JINKUN CHEN其他文献
JAKE JINKUN CHEN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JAKE JINKUN CHEN', 18)}}的其他基金
Potentials of Epigenetic Molecules in Attenuating the Phenotypes of Periodontitis
表观遗传分子减轻牙周炎表型的潜力
- 批准号:
10736171 - 财政年份:2023
- 资助金额:
$ 69.91万 - 项目类别:
Therapeutic Potentials of a New Long Noncoding RNA in Diabetic Bone Wound Repair
新型长非编码 RNA 在糖尿病骨伤口修复中的治疗潜力
- 批准号:
10684848 - 财政年份:2022
- 资助金额:
$ 69.91万 - 项目类别:
A Long Noncoding RNA Amerliorates Periodontitis via Distinct Epigenetic Pathways
长非编码 RNA 通过独特的表观遗传途径改善牙周炎
- 批准号:
10526289 - 财政年份:2020
- 资助金额:
$ 69.91万 - 项目类别:
A Long Noncoding RNA Amerliorates Periodontitis via Distinct Epigenetic Pathways
长非编码 RNA 通过独特的表观遗传途径改善牙周炎
- 批准号:
10096175 - 财政年份:2020
- 资助金额:
$ 69.91万 - 项目类别:
Roles of Noncoding RNA in Bone Regeneration
非编码 RNA 在骨再生中的作用
- 批准号:
10251012 - 财政年份:2016
- 资助金额:
$ 69.91万 - 项目类别:
Nanolipidoids-Conjugated MicroRNA Enhance Oral and Cranial Bone Regeneration
纳米脂质结合的 MicroRNA 增强口腔和颅骨再生
- 批准号:
9106764 - 财政年份:2016
- 资助金额:
$ 69.91万 - 项目类别:
Alveolar Bone Regeneration in Diabetic Periodontitis
糖尿病牙周炎的牙槽骨再生
- 批准号:
10058838 - 财政年份:2016
- 资助金额:
$ 69.91万 - 项目类别:
Roles of Noncoding RNA in Bone Regeneration
非编码 RNA 在骨再生中的作用
- 批准号:
10468834 - 财政年份:2016
- 资助金额:
$ 69.91万 - 项目类别:
Therapeutic Strategies for Treating Type 2 Diabetes Mellitus -Associated Periodon
治疗 2 型糖尿病相关牙周病的治疗策略
- 批准号:
8184470 - 财政年份:2011
- 资助金额:
$ 69.91万 - 项目类别:
相似海外基金
Developing a Young Adult-Mediated Intervention to Increase Colorectal Cancer Screening among Rural Screening Age-Eligible Adults
制定年轻人介导的干预措施,以增加农村符合筛查年龄的成年人的结直肠癌筛查
- 批准号:
10653464 - 财政年份:2023
- 资助金额:
$ 69.91万 - 项目类别:
Doctoral Dissertation Research: Estimating adult age-at-death from the pelvis
博士论文研究:从骨盆估算成人死亡年龄
- 批准号:
2316108 - 财政年份:2023
- 资助金额:
$ 69.91万 - 项目类别:
Standard Grant
Determining age dependent factors driving COVID-19 disease severity using experimental human paediatric and adult models of SARS-CoV-2 infection
使用 SARS-CoV-2 感染的实验性人类儿童和成人模型确定导致 COVID-19 疾病严重程度的年龄依赖因素
- 批准号:
BB/V006738/1 - 财政年份:2020
- 资助金额:
$ 69.91万 - 项目类别:
Research Grant
Transplantation of Adult, Tissue-Specific RPE Stem Cells for Non-exudative Age-related macular degeneration (AMD)
成人组织特异性 RPE 干细胞移植治疗非渗出性年龄相关性黄斑变性 (AMD)
- 批准号:
10294664 - 财政年份:2020
- 资助金额:
$ 69.91万 - 项目类别:
Sex differences in the effect of age on episodic memory-related brain function across the adult lifespan
年龄对成人一生中情景记忆相关脑功能影响的性别差异
- 批准号:
422882 - 财政年份:2019
- 资助金额:
$ 69.91万 - 项目类别:
Operating Grants
Modelling Age- and Sex-related Changes in Gait Coordination Strategies in a Healthy Adult Population Using Principal Component Analysis
使用主成分分析对健康成年人群步态协调策略中与年龄和性别相关的变化进行建模
- 批准号:
430871 - 财政年份:2019
- 资助金额:
$ 69.91万 - 项目类别:
Studentship Programs
Transplantation of Adult, Tissue-Specific RPE Stem Cells as Therapy for Non-exudative Age-Related Macular Degeneration AMD
成人组织特异性 RPE 干细胞移植治疗非渗出性年龄相关性黄斑变性 AMD
- 批准号:
9811094 - 财政年份:2019
- 资助金额:
$ 69.91万 - 项目类别:
Study of pathogenic mechanism of age-dependent chromosome translocation in adult acute lymphoblastic leukemia
成人急性淋巴细胞白血病年龄依赖性染色体易位发病机制研究
- 批准号:
18K16103 - 财政年份:2018
- 资助金额:
$ 69.91万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Doctoral Dissertation Research: Literacy Effects on Language Acquisition and Sentence Processing in Adult L1 and School-Age Heritage Speakers of Spanish
博士论文研究:识字对西班牙语成人母语和学龄传统使用者语言习得和句子处理的影响
- 批准号:
1823881 - 财政年份:2018
- 资助金额:
$ 69.91万 - 项目类别:
Standard Grant
Adult Age-differences in Auditory Selective Attention: The Interplay of Norepinephrine and Rhythmic Neural Activity
成人听觉选择性注意的年龄差异:去甲肾上腺素与节律神经活动的相互作用
- 批准号:
369385245 - 财政年份:2017
- 资助金额:
$ 69.91万 - 项目类别:
Research Grants