Mapping the joint-nerve interactome of the knee

绘制膝关节的关节神经相互作用组图

• 批准号: 10861323
• 负责人: Martin K Lotz
• 金额: $ 122.35万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-13 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10861323
• 关键词: ATAC-seq; Address; Age; Antibodies; Atlases; Bilateral; Blood Vessels; Cells; Chronic low back pain; Connective Tissue; Degenerative polyarthritis; Disease; Facet joint structure; Female; Funding; Gene Expression Profile; Generations; Genetic Transcription; Goals; Human; Intervertebral disc structure; Joints; Knee; Knee Osteoarthritis; Knee joint; Low Back Pain; Maps; Methods; Molecular; Molecular Analysis; Muscle; Nerve; Neurons; Nociceptors; Pain; Parents; Pathologic; Phase; Population; Price; Proprioceptor; Proteins; Research; Research Personnel; Resolution; Sensory; Small Nuclear RNA; Spatial Distribution; Spinal Ganglia; Structure; Temporomandibular Joint; Texas; Tissue Banks; Tissue Donors; Tissues; Universities; Vertebral column; Work; aged; axon guidance; cell type; chronic pain; epigenome; gene regulatory network; human old age (65+); insight; intervertebral disk degeneration; knee pain; male; mouse model; nerve supply; neural; neurotrophic factor; novel; parent grant; programs; therapeutic target; three-dimensional modeling; tissue degeneration; transcriptome; transcriptome sequencing; transcriptomics; vertebra body

ABSTRACT This supplement addresses are proposed studies are in the context of spine tissue damage and chronic low back pain (LBP). The goals of the parent grant are to construct 3D models of the sensory innervation of the knee, compose a cell atlas in which knee afferents are transcriptionally profiled at a single cell resolution, and document the nerve-joint cell interactome at the transcriptional level. The supplement substantially expands the scope and potential impact of the parent program by examining mechanisms of intervertebral disc (IVD) degeneration (IDD), facet joint (FJ) osteoarthritis (OA) and the interaction of these tissues with neurons in the generation of low back pain. The inclusion of the FJ also extends the portfolio of joints (knee and temporomandibular joints) that are currently being investigated in the RE-JOIN consortium. The team includes investigators at Rush University (PI Dr. Anne-Marie Malfait) and Scripps Research (PI Dr. Martin Lotz) in the funded UC2 project for the analysis of knee joints and adds new methods for the analysis of IVD and FC degeneration and the team at the University of Texas, Dallas (PI Dr. Theodore Price) adds expertise in the analysis of dorsal root ganglia (DRG). The team at Scripps has a long-standing program on mechanisms of knee OA and performed prior work on mechanisms of IDD, using mouse models and human spines. Omics analyses were applied to define cell populations and their gene regulatory networks in healthy and degenerated IVD. The team at Rush is a leader in the analysis of pain mechanisms in OA and has expertise in the analysis of neural structures in knee joints and in the analysis of chronic pain mechanisms. The two teams are working together in the funded RE-JOIN project about knee pain. Our unique approach is to examine spine and knee tissues from the same young healthy and older donors with OA and IDD for innervation, transcriptome and epigenome at tissue, single cell, and spatial levels. The integrative analysis of neural and connective tissue changes during IDD will reveal critical interactions that promote tissue damage and pain.

摘要 本补充说明提出的研究是在脊柱组织损伤和慢性低血压的背景下进行的 背痛(LBP)。父母赠款的目标是构建膝关节感觉神经的3D模型， 编写一份细胞图谱，其中膝盖传入以单一细胞分辨率转录描述，并记录 神经-关节细胞在转录水平上的相互作用。 该副刊通过审查，大大扩大了母项目的范围和潜在影响 椎间盘退行性变(IDD)、小关节(FJ)、骨关节炎(OA)和关节突关节病变的发病机制 在腰痛的产生过程中，这些组织与神经元的相互作用。FJ的加入也扩大了 目前在RE-Join中正在调查的关节组合(膝关节和颞下颌关节) 财团。 该团队包括拉什大学(Pi Dr.Anne-Marie Malfait)和斯克里普斯研究公司(Scripps Research)的研究人员。 Martin Lotz)在被资助的UC2项目中用于膝关节分析，并增加了新的分析方法 得克萨斯大学达拉斯分校的团队(派西奥多·普莱斯博士)增加了专业知识 在背根神经节(DRG)的分析中。斯克里普斯的团队有一个关于机械的长期项目 并使用小鼠模型和人类脊柱对缺铁性骨病的机制进行了先前的工作。组学 应用分析来确定健康和退行性疾病患者的细胞群体及其基因调控网络 IVD。Rush的团队在分析OA的疼痛机制方面处于领先地位，并在分析方面拥有专业知识 在膝关节的神经结构和慢性疼痛机制的分析中。这两个团队正在合作。 共同参与了关于膝盖疼痛的重新加入项目。我们独特的方法是检查脊柱和膝盖 来自相同的年轻的，健康的和老年的患有骨性关节炎和缺碘的捐赠者的组织，用于神经支配，转录组和 组织、单细胞和空间水平的表观基因组。神经结缔组织的综合分析 IDD期间的变化将揭示促进组织损伤和疼痛的关键相互作用。