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.

抽象的 本补充说明了在脊柱组织损伤和慢性低血压背景下拟议的研究 背痛（LBP）。家长资助的目标是构建膝盖感觉神经支配的 3D 模型， 撰写细胞图谱，其中以单细胞分辨率对膝部传入神经进行转录分析，并记录 转录水平的神经关节细胞相互作用组。 该补充文件通过审查显着扩大了母计划的范围和潜在影响 椎间盘（IVD）退变（IDD）、小关节（FJ）骨关节炎（OA）的机制 这些组织与神经元的相互作用导致腰痛的产生。 FJ 的加入也延伸了 目前正在 RE-JOIN 中研究的关节组合（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）和斯克里普斯研究所（PI Dr. Anne-Marie Malfait）的研究人员。 Martin Lotz）在资助的 UC2 项目中进行膝关节分析，并添加了新的分析方法 IVD 和 FC 变性以及德克萨斯大学达拉斯分校的团队（PI Dr. Theodore Price）增加了专业知识 在背根神经节（DRG）的分析中。斯克里普斯团队有一个关于机制的长期计划 膝 OA 的研究，并使用小鼠模型和人类脊柱对 IDD 机制进行了前期研究。组学 应用分析来定义健康和退化的细胞群及其基因调控网络 体外诊断。 Rush 团队是 OA 疼痛机制分析领域的领导者，拥有分析方面的专业知识 膝关节神经结构和慢性疼痛机制分析。两个团队正在努力 一起参与有关膝盖疼痛的 RE-JOIN 资助项目。我们独特的方法是检查脊柱和膝盖 来自同一年轻健康和老年 OA 和 IDD 捐献者的组织，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。神经和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。